case study for diabetes mellitus type 2

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Published: 17 January 2024

Nutrient patterns and risk of diabetes mellitus type 2: a case-control study

Morteza haramshahi 1 ,
Thoraya Mohamed Elhassan A-Elgadir 2 ,
Hamid Mahmood Abdullah Daabo 3 ,
Yahya Altinkaynak 4 ,
Ahmed Hjazi 5 ,
Archana Saxena 6 ,
Mazin A.A. Najm 7 ,
Abbas F. Almulla 8 ,
Ali Alsaalamy 9 &
Mohammad Amin Kashani 10

BMC Endocrine Disorders volume 24 , Article number: 10 ( 2024 ) Cite this article

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Backgrounds

Although the significance of diet in preventing or managing diabetes complications is highlighted in current literature, there is insufficient evidence regarding the correlation between nutrient patterns and these complications. The objective of this case-control study is to investigate this relationship by analyzing the dietary intake of nutrients in participants with and without type 2 diabetes (T2D).

A case-control study was conducted at the Tabriz Center of Metabolism and Endocrinology to investigate the relationship between nutrient patterns and type 2 diabetes (T2D). The study enrolled 225 newly diagnosed cases of T2D and 225 controls. The dietary intake of nutrients was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Principal component analysis using Varimax rotation was used to obtain nutrient patterns. Logistic regression analysis was performed to estimate the risk of T2D.

The participants’ mean (SD) age and BMI were 39.8 (8.8) years and 27.8 (3.6) kg/m2, respectively. The results identified three major nutrient patterns. The first nutrient pattern was characterized by high consumption of sucrose, animal protein, vitamin E, vitamin B1, vitamin B12, calcium, phosphorus, zinc, and potassium. The second nutrient pattern included fiber, plant protein, vitamin D, Riboflavin, Vitamin B5, copper, and Magnesium. The third nutrient pattern was characterized by fiber, plant protein, vitamin A, riboflavin, vitamin C, calcium, and potassium. Individuals in the highest tertile of nutrient pattern 3 (NP3) had a lower risk of T2D compared to those in the lowest tertile after adjusting for confounders. The odds ratio was 0.52 with a 95% confidence interval of 0.30–0.89 and a P_trend of 0.039.

This study found that conforming to a nutrient pattern consisting of plant protein, vitamin C, vitamin A, vitamin B2, potassium, and calcium is linked to a lower likelihood of developing T2D.The initial results suggest that following a nutrient pattern that includes these nutrients may reduce the risk of T2D. However, further research is required to confirm the relationship between nutrient patterns and T2D.

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Type 2 diabetes is a significant concern for public health in developed nations. It leads to high rates of illness and death and places a significant financial burden on healthcare systems [ 1 , 2 ]. In the past few decades, there has been a sharp increase in the occurrence of diabetes, and is expected to continue increasing, with an estimated 693 million people living with the disease by 2045 [ 1 ]. Complications associated with type 2 diabetes can also contribute to premature death. A concerning aspect of the disease is that a significant proportion of cases (40%) go undetected [ 3 ], and there is also an increasing prevalence of prediabetes, which raises the risk of developing type 2 diabetes and other chronic diseases [ 1 ].

The connection between diet and type 2 diabetes has been extensively studied, including the examination of dietary patterns and individual foods or nutrient patterns [ 4 , 5 , 6 , 7 ]. Various sources have suggested that chronic diseases may be influenced by a combination of nutrients [ 8 ]. In the field of nutritional epidemiology, the examination of dietary patterns has emerged as a viable approach to investigate the correlation between diet and disease. This method involves using statistical techniques to combine multiple foods or nutrients into dietary or nutrient patterns, which are believed to provide a more detailed understanding of the connection between diet and disease. It has been suggested that the impact of individual nutrients or foods on chronic disease may be too subtle to detect, but their collective effect within a pattern may be more indicative [ 9 ].

There have been some recent studies examining the effect of nutrient patterns on chronic disease such as, non-alcoholic fatty liver, breast and gastric cancer, Polycystic Ovary Syndrome (PCOs) and metabolic syndrome [ 10 , 11 , 12 , 13 , 14 ]. For example, it was found that a nutrient pattern consisting mainly of protein, carbohydrates, and various sugars was linked to a higher risk of Metabolic Syndrome (MetS) in both men and women, whereas a pattern characterized by copper, selenium, and several vitamins was linked to greater odds of MetS [ 14 ]. A prospective study conducted among participants of the Tehran Lipid and Glucose Study indicates that a nutrient pattern rich in vitamin A, vitamin C, vitamin B6, potassium, and fructose is associated with a reduced risk of insulin-related disorders [ 15 ]. Although there have been limited investigations on the connection between nutrient patterns and the likelihood of developing diabetes, the present study seeks to explore this relationship by analyzing the adherence to different nutrient patterns and its effect on the risk of type 2 diabetes.

Study population

This study utilized a case-control design and involved participants between the ages of 18 and 60 who had been diagnosed with type 2 diabetes within the previous six months based on specific glucose level criteria (FBS levels of ≥ 126 mg/dl and 2 h-PG levels of ≥ 200 mg/dl [ 17 ]). Healthy individuals within the same age range were also included, with specific glucose level criteria (FBS levels of < 100 mg/dl and 2 h-PG levels of < 200 mg/dl [ 17 ]). The study excluded individuals with certain chronic diseases, Type 1 Diabetes, gestational diabetes, those following specific dietary patterns or taking certain medications, pregnant and breastfeeding women, those with a family history of diabetes or hypertension, and those who did not complete the food frequency questionnaire (more than 35 items) or whose reported energy intake was outside of a specific range (range of 800–4200 kcal [ 18 ]).

This study enrolled 450 adult participants, with 225 individuals in the case group and 225 in the control group. The case group was selected using a simple sampling method from patients diagnosed with diabetes at the Tabriz Center of Metabolism and Endocrinology as a referral center affiliated to tabriz University of Medical Sciences from January 2021 to March 2022, as well as through a two-stage cluster sampling method among patients referred to private endocrinologists to enhance the sample’s external validity. Participants in the control group were also selected through a two-stage cluster sampling method from individuals who had undergone blood glucose checkups at the Tabriz Center of Metabolism and Endocrinology, a referral center affiliated with Tabriz University of Medical Sciences, within the past six months. All participants provided informed consent at the beginning of the study. The study was financially supported by Tabriz University of Medical Sciences and is related to project NO. 1400/63,145.

Dietary assessment

To collect dietary intake information, personal interviews and a semi-quantitative food frequency questionnaire (FFQ) consisting of 168 food items were used [ 16 ]. The FFQ asked about the frequency of consumption for each item over the course of one year, with the year before diagnosis for the case group and the year before the interview for the control group. Participants were also asked about the frequency of consumption (per day, week, month, or year) for each type of food. to ensure consistency in measurements, a nutritionist provided instructions on converting the size of reported food items from household measures to grams using four scales. The quantity of food consumed by each individual was calculated based on their intake in grams and reported on a daily basis. The nutrient composition of all foods was derived by using modified nutritionist IV software.

Nutrient pattern assessment

We conducted factor analyses using a comprehensive set of 34 nutrients, encompassing various macronutrients, micronutrients, and other dietary components. These included sucrose, lactose, fructose, fiber, animal protein, plant protein, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, as well as an array of vitamins and minerals such as A, D, E, K, C, thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), folate (B9), B12, calcium, phosphorus, iron, zinc, copper, magnesium, manganese, chromium, selenium, sodium, potassium, and caffeine. The dietary intake of these 34 nutrients per 1,000 Kcal of energy intake was computed and utilized as input variables. Subsequently, nutrient patterns (NPs) were derived through principal component analysis (PCA) with varimax rotation, based on the correlation matrix. Factor scores for each participant were then calculated by aggregating the frequency of consumption and multiplying it by the factor loadings across all 34 nutrients. To assess the statistical correlation between variables and evaluate the adequacy of the sample size, we employed the Bartlett test of sphericity ( P < 0.001) and the Kaiser-Mayer-Olkin test (0.71), respectively.

Assessment of other variables

To obtain the participants’ anthropometric measurements, weight and height were measured using a seca scale, and the participants’ BMI was determined by dividing their weight in kilograms by the square of their height in meters. Waist circumference was measured using a metal anthropometric tape, and the participants’ hip circumference was measured using a metal anthropometric tape while standing [ 17 ]. Daily physical activity was measured using a physical activity questionnaire [ 18 ], and personal questioning was employed to gather information on population and socioeconomic characteristics, including marital status, academic degree, and smoking.

Statistical analysis

Statistical analysis was performed using the Statistical Package Software for Social Science, version 21. The normality of the data was assessed using Kolmogorov-Smirnov’s test and histogram chart. The characteristics and dietary intakes of the case and control groups were presented as mean ± SD or median and frequency (percentages). Independent sample t-tests and chi-square tests were used to compare continuous and categorical variables, respectively, between the case and control groups.

The participants’ mean (SD) age and BMI were 39.8 (8.8) years and 27.8 (3.6) kg/m2, respectively. The mean (SD) BMI in the case group was 30.5 ± 4.1, and in the control group, it was 25.2 ± 3.2 kg/m2. The mean (SD) physical activity in the case group was 1121 ± 611 MET/min/week, and in the control group, it was 1598 ± 940 MET/min/week. There were significant differences in BMI and physical activity between the two groups. The mean (SD) waist circumference in the case group was 109.32 ± 10.28 cm, and in the control group, it was 87.25 ± 9.35 cm. The mean (SD) hip circumference in the case group was 107.25 ± 8.61 cm, and in the control group, it was 91.44 ± 6.17 cm. The study identified three primary nutrient patterns (NPs) with eigenvalues greater than 2. Table 1 displays the factor loadings for nutrient patterns, which accounted for 56.11% of the total nutrient variation. The high intake of sucrose, animal protein, phosphorus, zinc, potassium, calcium, vitamin E, vitamin B1 and vitamin B12 were the distinguishing features of the first pattern. The second nutrient pattern was positively associated with copper, magnesium, fiber, vitamin D, B2, B5 and plant protein but had a negative correlation with lactose and saturated fatty acids. On the other hand, the high intake of fiber, vitamin A, B2, vitamin C, plant protein and potassium were the distinguishing features of the third pattern.

The following are the characteristics of T2D patients compared to the control group, as shown in Table 2 : Higher BMI, More likely to be smokers, Lower physical activity levels, higher FBS, HbA1C, Insulin ( p < 0.05). Other variables did not differ significantly between the two groups ( p > 0.05). Additionally, T2D patients had a greater intake of energy and vitamin B3 but consumed less plant protein, vitamin A, vitamin E, vitamin B2, and zinc ( p < 0.05).

Table 3 summarizes the partial correlation coefficient between NPs and food sources, with NP1 showing a strong positive correlation with low-fat dairy, NP2 with refined grains, and NP3 with fruits and vegetables.

Table 4 demonstrates the relationships between NPs and T2D. After adjusting for age and sex, there was no significant link between each nutrient pattern (NP) and T2D. However, when adjusting for other factors such as BMI, physical activity, smoking, and energy intake, individuals in the highest tertile of NP1 and NP2 did not show a significant association with T2D compared to those in the lowest tertile. On the other hand, those in the highest tertile of NP3 had a lower probability of developing T2D than those in the lowest tertile (OR: 0.52, 95%CI: 0.30–0.89, P_trend = 0.039).

In this study, three major NPs were identified. After adjusting for potential confounders, we observed a significant inverse association between the Third NP and the odds of T2D. The high intake of fiber, vitamin A, B2, vitamin C, plant protein and potassium were the distinguishing features of the third pattern.

Dietary patterns, such as healthy, Mediterranean, traditional, and Western dietary patterns, have recently received significant attention in studying the connection between diet and health. When looking at the relationship between nutrients and disease incidence, it is more challenging to evaluate when considering individual foods and the metabolism of all nutrients together [ 19 ]. It is therefore more effective to take a broader view and consider diet as a whole. Dietary and nutrient patterns can have a greater impact on health than specific nutrients or nutritional groups. There is supporting evidence that links high calorie or high glycemic index foods with an increased risk of T2D. The quality of one’s diet is also associated with the risk, progression, and side effects of T2D [ 20 ]. Establishing a desirable food pattern has become a priority in public health efforts to prevent T2D. By studying dietary and nutrient patterns, we can gain a comprehensive understanding of an individual’s overall diet beyond just the consumption of specific nutrients and food groups. Moreover, it is easier for people to understand health recommendations when presented as dietary patterns rather than focusing solely on individual nutrients [ 19 ].

A previous cross-sectional study investigated the relationship between NPs and fasting glucose and glycated hemoglobin levels among apparently healthy black South Africans. The study stratified 2,010 participants by gender and urban/rural status and identified three nutrient patterns per stratum. In rural women, a nutrient pattern driven by starch, dietary fiber, and B vitamins was significantly associated with lower fasting glucose and glycated hemoglobin levels. A nutrient pattern that included vitamin B1, zinc, and plant protein was linked to notable decreases in glycated hemoglobin and fasting glucose levels in rural men. These findings suggest that nutrient patterns that are plant-based are linked to lower levels of fasting glucose and glycated hemoglobin [ 21 ].

Iwasaki et al. found that specific nutrient patterns were associated with lower risks of MetS. One nutrient pattern high in potassium, fiber, and vitamins, while another pattern high in vitamin B2, saturated fatty acids and calcium [ 22 ]. A recent study found that a nutrient pattern characterized by high intake of calcium, potassium, fats, cholesterol, vitamins B2, B12, A, D, K and C was positively linked to MetS [ 23 ]. Salehi-Sahlabadi et al. found that adhering to a nutrient pattern rich in potassium, vitamin A, fructose, vitamin C and vitamin B6 was negatively associated with the likelihood of NAFLD [ 11 ]. A nutrient pattern high in potassium, vitamin A, vitamin B6, vitamin C and fructose was associated with a reduced risk of hyperinsulinemia, IR, and dyslipidemia among participants in Tehran, according to a prospective study [ 11 , 24 , 25 ].

Due to several variations among studies exploring NPs linked to chronic diseases, including differences in the number of nutrients, populations, study designs and outcomes there has been a considerable diversity in the identified NPs, with only a few NPs being replicated across studies. Our study is the first of its kind to explore the correlation between nutrient patterns and T2D in this context.

In our study, there was no association between NPs 1 and 2 and T2D. This lack of correlation may be attributed to the absence of harmful nutrients or food categories linked to diabetes in these NPs. NP3 in this study, unlike other NPs, is positively associated with beneficial food groups such as nuts, fruits, plant oil and vegetables, and negatively associated with unhealthy food groups like red-processed meat, snacks, high-fat dairy and refined grains. A recent systematic review and meta-analysis found that individuals who consumed higher amounts of fruits and vegetables had a lower risk of developing type 2 diabetes [ 26 ]. Moreover, the consumption of vegetables was found to have an inverse relationship with ALT, TC and LDL levels among adults, while fruit consumption was associated with a positive reduction in visceral fat [ 27 , 28 ]. Another study suggested that an increased intake of vegetables and fruits could potentially lower the risk of MetS [ 29 ]. According to a study, greater nut consumption was significantly linked to a reduced prevalence of T2D [ 30 ]. Consuming fruits and vegetables is a crucial component of a healthful dietary pattern that can lower the risk of type 2 diabetes [ 31 ]. On the other hand, Consuming a Western dietary pattern, which primarily consists of fast foods, high-fat dairy, refined grains, soft drinks and processed meat has been found to be correlated with an increased risk of type 2 diabetes [ 31 ].

Several mechanisms have been identified that explain the positive associations between the components of NP 3 and T2D or its risk factors. Vitamin intake has been shown to play a role in the development of T2D through various pathways. Consuming vitamin C has been found to have beneficial effects in reducing the risk of type 2 diabetes mellitus. These effects can be attributed to the following actions of vitamin C: vasodilator, cytoprotective, platelet anti-aggregator and anti-mutagenic. To achieve this, the body increases the production of several substances including prostaglandin E1, PGI2, endothelial nitric oxide, and lipoxin A4. Additionally, the body restores the Arachidonic Acid content to normal levels [ 32 ]. Vitamin A has a multifaceted role in cell regulation beyond its antioxidant function. It contributes to gene regulation, epithelial cell integrity, and resistance to infection. Research suggests that vitamin A also enhances antioxidant enzyme function in the body. Research has indicated a link between vitamin A deficiency and type 2 diabetes mellitus (T2DM), which suggests that vitamin A may have a role in the biology of T2DM [ 33 ]. Moreover, a meta-analysis has found that replacing animal protein with plant protein can lead to minor improvements in glycemic control for individuals with diabetes [ 34 ]. According to a recent meta-analysis, increasing the consumption of fruits, especially berries, yellow vegetables, cruciferous vegetables, green leafy vegetables is associated with a lower risk of developing type 2 diabetes. These results support the recommendation to incorporate more fruits and vegetables into the diet as a way to prevent various chronic diseases, including type 2 diabetes [ 35 ]. A study showed that maintaining adequate potassium intake could regulate insulin secretion and carbohydrate metabolism, leading to the prevention of obesity and metabolic syndrome (MetS) [ 36 ].

A number of research studies conducted in the Western societies have shown that Western dietary pattern including higher intake of red meat, processed meat, and refined grains is significantly associated with increased risk of T2D [ 37 , 38 ]. For example, in the 12-years cohort prospective study, van Dam et al. investigated dietary pattern of 42,504 American white men at the age range of 40–75 years old using the FFQ. After controlling the confounders, the risk of T2D increased 60% in people adherent to the western-like dietary pattern [ 38 ]. The rapid process of change in lifestyle, diets, and physical activity that have been occurred as a result of extended urbanization, improved economic status, change of work pattern toward jobs, and change in the processes of producing and distributing nutrients during the recent years in developing countries have led people to more consumption of fast food and processed foods [ 20 ].

Significant research has been conducted on the impact of nutrient type and sequence on glucose tolerance. Multiple studies have shown that manipulating the sequence of food intake can enhance glycemic control in individuals with type 2 diabetes in real-life situations. The glucose-lowering effect of preload-based nutritional strategies has been found to be more pronounced in type 2 diabetes patients compared to healthy individuals. Moreover, consuming carbohydrates last, as part of meal patterns, has been proven to improve glucose tolerance and reduce the risk of weight gain [ 39 ]. Recent findings on meal sequence further emphasize the potential of this dietary approach in preventing and managing type 2 diabetes [ 40 ].

Several studies have shown that food from a short supply chain has a significant impact on metabolic syndrome. The length of the food supply chain is important in determining the risk of metabolic syndrome in a population [ 41 ]. Research indicates that people who consume food from short supply chains have a lower prevalence of metabolic syndrome compared to those who consume food from long supply chains. Specifically, food from short supply chains is associated with lower levels of triglycerides and glucose, which leads to a reduced occurrence of metabolic syndrome [ 42 ]. Adhering to the Mediterranean diet with a short supply chain is also found to significantly reduce the prevalence of metabolic syndrome. Therefore, these studies provide evidence that food from short supply chains positively affects metabolic parameters and the occurrence of metabolic syndrome [ 41 ].

The study we conducted presented several advantages. It was the first case-control research to investigate the correlation between nutrient patterns and the likelihood of developing type 2 diabetes (T2D). While numerous studies have explored the relationship between dietary patterns and diabetes, there is a scarcity of research specifically focusing on nutrient patterns in individuals with type 2 diabetes. Furthermore, the collection of dietary intake data was carried out through face-to-face interviews conducted by trained dieticians to minimize measurement errors. However, this study also had some limitations. Case-control studies are susceptible to selection and recall biases. Additionally, the use of factor analysis to identify patterns, and the potential influence of research decisions on the number of factors and nutrient factor loadings in each pattern, should be considered. Lastly, despite the use of a validated semi-quantitative FFQ (food frequency questionnaire), there remains a possibility of measurement error due to dietary recall. The study’s findings and limitations contribute to the ongoing discourse on the role of nutrient patterns in the development of T2D and the importance of considering these factors in future research and preventive strategies.

Conclusions

The results of this study indicate that conforming to a nutrient pattern consisting of plant protein, vitamin C, vitamin A, vitamin B2, potassium, and calcium is linked to a lower likelihood of developing T2D. Our investigation did not reveal any significant correlation between other nutrient patterns and T2D risk. However, additional research is necessary to authenticate these initial findings and establish the correlation between nutrient patterns and T2D.

Data availability

Upon reasonable request, the corresponding author can provide the datasets that were produced and analyzed during the current study.

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Acknowledgements

The researchers express their gratitude towards all the individuals who volunteered to take part in the study.

This research received no external funding.

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Faculty of medicine, Tabriz University of medical sciences, Tabriz, Iran

Morteza haramshahi

Department of clinical biochemistry, College of medicine, King Khalid University, Abha, Saudi Arabia

Thoraya Mohamed Elhassan A-Elgadir

Fharmacy Department, Duhok polytechnic, University Duhok, Kurdistan, Iraq

Hamid Mahmood Abdullah Daabo

Department of Medical Services and Techniques, Ardahan University, Ardahan, Turkey

Yahya Altinkaynak

Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Jeddah, Saudi Arabia

Ahmed Hjazi

Department of Management, Uttaranchal Institute of Management, Uttaranchal University, Dehradun, Uttarakhand, India

Archana Saxena

Pharmaceutical Chemistry Department, College of Pharmacy, Al-Ayen University, Thi-Qar, Iraq

Mazin A.A. Najm

College of technical engineering, The Islamic University, Najaf, Iraq

Abbas F. Almulla

College of technical engineering, Imam Ja’afar Al-Sadiq University, Al‐Muthanna, 66002, Iraq

Ali Alsaalamy

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

Mohammad Amin Kashani

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The study’s protocol was designed by M.K., M.H., and T.E., while H.A., Y.A., and A.H. carried out the research. A.S. analyzed the data and prepared the initial draft of the manuscript. M.N., A.FA., and A.A. interpreted the data and provided critical feedback on the manuscript. All authors reviewed and approved the final version of the manuscript.

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haramshahi, M., A-Elgadir, T.M.E., Daabo, H.M.A. et al. Nutrient patterns and risk of diabetes mellitus type 2: a case-control study. BMC Endocr Disord 24 , 10 (2024). https://doi.org/10.1186/s12902-024-01540-5

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Treatment of type 2 diabetes mellitus (T2DM) focuses on decreasing blood glucose, increasing insulin secretion, or countering insulin resistance. Treatment of symptoms, such as diabetic retinopathy, nephropathy, or neuropathy requires additional and involved patient education, medications, and therapies.

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Treatment of obesity and other symptoms of metabolic syndrome is essential. Exercise is an effective intervention because it reduces postprandial blood glucose levels, diminishes insulin requirements, lowers triglyceride and cholesterol levels, and increases the level of HDL cholesterol. Physical activity also aids in weight reduction. Diet modifications include restricted yet consistent caloric intake appropriate for ideal weight and activity level. Dietary counselling is through medical nutrition therapy (MNT) should focus on achieving biometric goals (McCance & Huether, 2014).

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Oral hypoglycemic medications are usually needed for optimal management of T2DM. Insulin may be need in later stages due to functional loss of beta cells of the pancreas (McCance & Huether, 2014).

Bariatric surgery may be indicated for patients who are morbidly obese and unresponsive to diet and exercise interventions. Currently, powerful evidence exists that shows bariatric surgery improves glycemic control in up to 80% of individuals with T2DM even before there is any significant weight loss (McCance & Huether, 2014).

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Case Study: A Patient With Uncontrolled Type 2 Diabetes and Complex Comorbidities Whose Diabetes Care Is Managed by an Advanced Practice Nurse

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Determinants of hypertension among diabetic patients in southern Ethiopia: a case-control study

Affiliations.

1 Department of Internal Medicine, School of Medicine, College of Health Sciences and Medicine, Wolaita Sodo University, Po.box 138, Sodo, Ethiopia. [email protected].
2 Department of Epidemiology and Biostatistics, School of Public Health, College of Health Sciences and Medicine, Wolaita Sodo University, Po.box 138, Sodo, Ethiopia.
3 Department of Internal Medicine, School of Medicine, College of Health Sciences and Medicine, Wolaita Sodo University, Po.box 138, Sodo, Ethiopia.
4 School of Medicine, College of Health Sciences and Medicine, Wolaita Sodo University, Po.box 138, Sodo, Ethiopia.
PMID: 37138213
PMCID: PMC10157915
DOI: 10.1186/s12872-023-03245-4

Background: Hypertension, among diabetic patients, is a worldwide public-health challenge and a number one modifiable risk factor for other cardiovascular diseases and death. The prevalence of hypertension among the diabetic population is nearly twice of nondiabetic patients. Screening and prevention of risk factors for hypertension based on evidence from local studies is required to minimize the burden of hypertension among diabetic patients. This study is aimed at assessing the determinants of hypertension among diabetic patients in Wolaita Sodo University Comprehensive Specialized Hospital, Southern Ethiopia, 2022.

Methods: Facility-based unmatched case-control study design was conducted from March 15 to April 15, 2022, at the outpatient diabetic clinic, Wolaita Sodo University Comprehensive Specialized Hospital. A total of 345 diabetic patients were selected using systematic random sampling techniques. Data were collected using a structured questionnaire by interviewing and extracting from the medical chart of patients. Bivariate logistic regression followed by multiple logistic analysis was used to identify the determinants of hypertension among diabetic patients. A p-value less than 0.05 is considered to be statistically significant.

Results: The significant determinants of hypertension among diabetes patients were being overweight [AOR = 2.06, 95% CI (1.1, 3.89), P = 0.025], being obese [AOR = 2.64, 95% CI (1.22, 5.70), P = 0.013], lack of Moderate intensity exercise [AOR = 2.41, 95% CI (1.36,4.24), P = 0.002], age [AOR = 1.03, 95% CI (1.01, 1.06), P = 0.011], Type 2 diabetes mellitus [AOR = 5.05, 95% CI (1.28, 19.88), P = 0.021], duration of diabetes mellitus ≥ 6 years [AOR = 7.47, 95% CI (2.02, 27.57), P = 0.003], diabetic nephropathy [AOR = 3.87, 95% CI (1.13, 13.29), P = 0.032], and urban residence [AOR = 2.11, 95% CI (1.04,4.29), P = 0.04].

Conclusion: Being overweight and obese, lack of moderate-intensity exercise, age, type 2 diabetes mellitus, duration of Diabetes ≥ 6 years, presence of diabetic nephropathy, and being urban residents were significant determinants of hypertension among diabetic patients. These risk factors can be targeted by health professionals for prevention and earlier detection of hypertension among diabetic patients.

Keywords: Blood pressure; Cardiovascular disease; Diabetes mellitus; Ethiopia; Hypertension.

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Remnant cholesterol and the risk of diabetic nephropathy progression to end-stage kidney disease in patients with type 2 diabetes mellitus: a longitudinal cohort study

Original Article
Open access
Published: 12 July 2024

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Yuancheng Zhao 1 na1 ,
Ke Liu 1 na1 ,
Yutong Zou 1 na1 ,
Yucheng Wu 1 ,
Jia Yang 1 ,
Xiang Xiao 1 ,
Xuegui Ju 1 ,
Qin Yang 1 ,
Yanlin Lang 1 &
Fang Liu 1 , 2

Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease (ESKD). Remnant cholesterol has been investigated as a predictor for the progression of DN in type 1 diabetes mellitus patients, as well as the incidence of DN in type 2 diabetes mellitus (T2DM) patients. This study aimed to evaluate the longitudinal relationship between baseline remnant cholesterol and kidney outcomes using a Chinese T2DM with biopsy-confirmed DN cohort.

We included 334 patients with T2DM and biopsy-confirmed DN during 2010–2019 West China Hospital T2DM-DN cohort. Remnant cholesterol was defined by Martin-Hopkins equation. Patients were divided into four groups based on the median (IQR) remnant cholesterol concentration at the time of renal biopsy. The kidney outcome was defined as ESKD, which was defined as the need for chronic kidney replacement therapy or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 . The relationship between remnant cholesterol and kidney outcome was analyzed using the Kaplan‒Meier method and Cox regression analysis.

The mean age was 51.1 years, and 235 (70%) were men. During follow-up, a total of 121 (36.2%) patients reached ESKD. The Kaplan‒Meier analysis showed that patients in the highest quartile (quartile 4) group had lower cumulative renal survival (log-rank test, p = 0.033) and shorter median renal survival time [34.0 (26.4–41.6) vs. 55.0 (29.8–80.2) months] than patients in the lowest quartile (quartile 1) group. By univariate analysis, the high remnant cholesterol group was associated with a higher risk of progression to ESKD. Moreover, the risk of progression to ESKD in the highest quartile was still 2.857-fold (95% CI 1.305–6.257, p = 0.009) higher than that in the lowest quartile, and one-SD increase of remnant cholesterol was associated with a higher risk (HR = 1.424; 95% CI 1.075–1.886, p = 0.014) of progression to ESKD, after adjusted for confounding factors.

Conclusions

High remnant cholesterol is independently associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive marker of ESKD.

Clinical relevance

Calculated remnant cholesterol has the advantages of being economical and clinically accessible. Moreover, to our knowledge, there are no longitudinal cohort studies for investigating the risk of progression of T2DM-DN to ESKD. In our study, higher remnant cholesterol was associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive predictor of ESKD.

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Introduction

The prevalence of diabetes has gradually increased over the past decades. According to the 10th edition of the IDF Diabetes Atlas [ 1 ], in 2021, it is estimated that 537 million people have diabetes and over 6.7 million people aged 20–79 will die from diabetes-related causes. Diabetes not only damages the physical and mental health of people but also causes a great economic burden. Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage kidney disease (ESKD) in developing and some developed countries [ 2 , 3 ]. There are some factors that are prognostic markers for DN prognosis, such as proteinuria and estimated glomerular filtration rate (eGFR) [ 4 ], however, even after improving many controllable risk factors, patients still have residual risks for ESKD and cardiovascular events.

Dyslipidemia is extremely common in patients with type 2 diabetes mellitus (T2DM). Previous studies have indicated that dyslipidemia is strongly associated with an increased risk of cardiovascular disease (CVD) in patients with T2DM [ 5 ]. A growing body of evidence suggests a strong atherogenicity of the cholesterol in triglyceride-rich lipoproteins (TRLs), also termed remnant cholesterol (RC) that is composed of very-low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs) in the fasting state and of VLDL, IDL and chylomicron remnants in the non-fasting state [ 6 ]. Numerous studies have shown that RC is strongly associated with adverse cardiovascular events and mortality in the general population and T2DM patients [ 7 , 8 , 9 ]. In addition, recent studies have shown that RC is associated with the incidence of chronic kidney disease (CKD) in the general population [ 10 ], the incidence of DN in T2DM patients [ 11 ], and the progression of DN and diabetic retinopathy (DR) in type 1 diabetes mellitus (T1DM) patients [ 12 ]. However, there are few studies on the relationship between RC and the progression to ESKD in patients with T2DM and biopsy-proven DN.

Therefore, this study aimed to evaluate the relationship between RC and the progression to ESKD in patients with T2DM-DN.

Patient selection and study design

This study included adult patients with T2DM who underwent kidney biopsy from 2010 to 2019 at the West China Hospital of Sichuan University. All patients were followed up for at least 1 year. The exclusion criteria were as follows: 1) combined with systemic disease and 2) reached ESKD before kidney biopsy (Fig. 1 ). Diabetes is diagnosed based on American Diabetes Association criteria [ 13 ]. The kidney biopsy indicators in T2DM patients are as follows: sudden onset of significant albuminuria, rapid deterioration of renal function (decrease in estimated glomerular filtration rate (eGFR), the eGFR was calculated using the CKD-EPI equation [ 14 ], absence of DR, or presence of active urinary sediment. The pathological diagnosis of DN was confirmed by at least two pathologists in the Pathology Department of West China Hospital. The definition of renal pathological features is based on the 2010 Society for Renal Pathology Classification [ 15 ]. All patients provided written informed consent, and this study was approved by the institutional review board at the West China Hospital of Sichuan University.

Flowchart of study participants

Clinical and pathological features

Baseline clinical data were obtained by interview and anthropometrics, including sex, age, body mass index, duration of diabetes, blood pressure, dyslipidemia, and medication history. Urine samples and blood samples were obtained using a biochemical automated analyzer (Cobas Intera 400 Plus, Roche, Basel, Switzerland) and included blood creatinine, triglycerides, cholesterol, HbA1c, fasting glucose, and 24-hour urine protein. Triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol were directly measured using a Triglyceride Assay Kit (GPO-PAP Method), Cholesterol Kit (CHOD-PAP Method), low-density lipoprotein (LDL) cholesterol Kit (Surfactant Assay), and high-density lipoprotein (HDL) Cholesterol Kit (CAT Assay) by a BECKMAN COULTER AU5800 Series Chemistry Analyzer. Dyslipidemia was defined as triglycerides >2.3 mmol/L, total cholesterol ≥6.2 mmol/L, LDL cholesterol >4.1 mmol/l, HDl. cholesterol <1.0 mmol/l, or any lipid lowering medication or self-reported history of dyslipidemia based on the Guidelines on Prevention and Treatment of Dyslipidemia for Chinese Adults [ 11 ]. Remnant cholesterol was defined by Martin-Hopkins equation [ 16 ], calculation as total cholesterol - LDL cholesterol - HDL cholesterol. Total cholesterol and HDL in the formulas are usually obtained from direct measurements, and LDL can be derived from direct measurements or formulas.

Renal pathology specimens were obtained by needle and evaluated by light microscopy, electron microscopy, and immunofluorescence to assess kidney pathological features, which is known as the Renal Pathology Society classification.

Kidney outcomes

The kidney outcome was defined by the progression to ESKD, which was defined as the need for chronic kidney replacement therapy or eGFR <15 mL/min/1.73 m 2 over the 3 months [ 17 ].

Statistical analysis

R software version 4.0.2 was used to perform all statistical analyses. Continuous variables are presented as the mean ± standard deviation or median and quartile range according to normality. Differences between groups were assessed by one-way ANOVA for normally distributed variables and nonparametric tests for skewed distributed variables, such as proportions, and the chi-square test for categorical variables. The correlation test was performed to analyze the associations between RC and DN. Kaplan‒Meier analysis was performed for kidney survival analysis using the log-rank test. Univariate and multivariate Cox analyses were used to examine the relationship between RC and renal outcomes. p values < 0.05 were considered to be significant.

Baseline clinical and pathological features

A total of 334 patients were included in the study (Fig. 1 ). At the time of the kidney biopsy, the mean age of the total cohort was 51.1 ± 9.3 years, 70% (235 in 334) were male, 86% (288 in 334) had hypertension, and 48% (159 in 334) had a history of smoking. The mean BMI of patients was 25.6 ± 3.7 kg/m 2 , the mean serum albumin was 34.5 ± 7.9 g/L, and the mean hemoglobin was 119.0 ± 24.1 g/L. The median duration of diabetes in the cohort was 96 (36–132) months, the median eGFR was 60.7 (44.1–92.6) ml/min/1.73 m 2 , and the median urinary protein excretion was 3.8 (1.8–7.0) g/d. Median triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol in the cohort were 1.8 (1.3, 2.4), 5.0 (4.2–6.1), 2.9 (2.2–3.7) and 1.2 (1.0–1.5) mmol/L, respectively. There are 262 (78.4%) had dyslipidemia, including 81 (97.6%) in Quartile 4. A total of 78.7% (263 in 334) of participants had a history of RAAS inhibitor use, and 58.1% (194 in 334) of the participants had a history of statin use. Baseline characteristics are presented in Table 1 .

In terms of pathological features, we studied this cohort according to the RPS classification. For the glomerular classification, 15 (4.5%) were in class I, 73 (21.8%) in class IIa, 44 (13.2%) in class IIb, 154 (46.1%) in class III, and 48 (14.4%) in class IV. Most patients had interstitial fibrosis and tubular atrophy (IFTA) (97.3%, 325/334), interstitial inflammation (95.5%, 319/334), arteriolar hyaline degeneration (92.5%, 209/334), and arteriosclerosis (92%, 207/334) in their renal biopsy samples (Table 2 ).

Relation between RC and clinicopathological features

Based on the median and quartile range of baseline RC concentrations, all patients were divided into four groups: Quartile 1: RC ≤ 0.46 mmol/L; Quartile 2: RC > 0.46 mmol/L and RC ≤ 0.68 mmol/L; Quartile 3: RC > 0.68 mmol/L and RC ≤ 1.02 mmol/L; and Quartile 4: RC > 1.02 mmol/L.

In this cohort, Quartile 1, Quartile 2, Quartile 3, and Quartile 4 had 25.1% (84 in 334), 25.7% (86 in 334), 24.3% (81 in 334), and 24.9% (83 in 334) patients, respectively. Patients in the Quartile 4 group had higher triglycerides, total cholesterol, and LDL-cholesterol levels and lower HDL-cholesterol levels. Patients in the Quartile 4 group had higher baseline fasting blood glucose compared to other groups, but the differences between the groups were not statistically significant. The histories of smoking and hypertension were similar among the four groups. Baseline age, BMI, duration of diabetes, HbA1c, eGFR, urinary protein excretion, hemoglobin, plasma albumin, insulin use, RAAS inhibitor use, statin use, and dyslipidemia were comparable in different groups (Table 1 ).

Regarding pathologic characteristics, patients in the Quartile 4 group had more severe arterial hyaline compared to other groups, but the differences between the groups were not statistically significant. The degree of glomerular lesions, interstitial fibrosis and tubular atrophy, interstitial inflammation, and arteriosclerosis were comparable in the different groups (Table 2 ).

RC and renal outcome of DN

At the end of the study, during a median follow-up of 27 (17–43) months, a total of 121 (36.2%) patients reached kidney outcomes. Patients in the Quartile 4 group had a shorter median renal survival time [34.0 (26.4–41.6) vs. 55.0 (29.8–80.2) months] than patients in the Quartile 1 group. The Kaplan‒Meier test indicated that patients in the quartile 4 group had worse cumulative kidney survival than those in the other groups (log-rank test, p = 0.033) (Fig. 2 ). For further study, we used the Cox proportional model. In univariate analysis, high RC was associated with worse renal outcomes, regardless of a continuous variable (HR = 1.223; 95% CI 1.037–1.442, p = 0.017) or categorical variable (HR = 1.784; 95% CI 1.073–2.966, p = 0.026). To limit confounding factors, first adjusting for age, sex, BMI, hypertension, smoking, HbA1c, history of insulin use, history of RAAS inhibitor use, history of statin use and dyslipidemia (Model 1), high RC levels were still associated with a higher risk of ESKD in both continuous (HR = 1.489; 95% CI 1.138–1.949, p = 0.004) and categorical RC (HR = 3.323; 95% CI 1.489–7.418, p = 0.003). After further correcting for eGFR and urinary protein excretion (Model 2), higher RC levels were still significantly associated with a higher risk of progression to ESKD in patients with T2DM and biopsy-proven DN in continuous (HR = 1.440; 95% CI 1.081–1.917, p = 0.013) and categorical RC (HR = 3.101; 95% CI 1.377- 6.987, p = 0.006). To account for the effect of pathology type, we corrected for RPS and IFTA, which usually have a greater impact on nephropathy, and in addition, we included arteriolar hyalinosis considering that it may be associated with RC (model 3). The findings were consistent with the previous ones, with high RC levels being associated with higher risk of progression to ESKD in both continuous (HR = 1.439; 95% CI 1.080–1.917, p = 0.013) and categorical studies (HR = 3.351; 95% CI 1.452 – 7.735, p = 0.005) (Table 3 ). Figure 3 showed the dose-response relationship between baseline RC and the risk of progression to ESKD.

Renal survival rate between patients in four groups by Kaplan–Meier. The event-free survival for end stage kidney diseases (log-rank test, p = 0.033)

Dose-response relationships of baseline remnant cholesterol with incidence of ESKD. Restricted cubic spline regression model was conducted using 3 knots. The blue line and blue area represent the hazard radios and the 95% confidence intervals for the spline model

This cohort study explored the longitudinal correlation between baseline remnant cholesterol and the progression to ESKD in patients with T2DM and biopsy-proven DN. Remnant cholesterol was a risk factor for DN progression to ESKD, independent of the traditional risk factors for ESKD, insulin use, RSSA inhibitor use, and statin use. In addition, patients with higher RC levels tended to have higher triglyceride, total cholesterol, and LDL-cholesterol levels, and lower HDL-cholesterol levels.

The previous study showed that higher remnant cholesterol is independently associated with an increased risk of prevalent CKD in a general middle-aged and elderly Chinese population [ 10 ]. Other studies showed that remnant cholesterol is independently associated with not only the risk of DN in T2DM patients [ 11 ] but also with the risk of the progression of DN and DR in T1DM patients [ 12 ]. Moreover, patients with higher remnant cholesterol levels tended to have higher triglyceride, total cholesterol, and LDL-cholesterol levels and lower HDL-cholesterol levels, regardless of general population, T2DM or T1DM patients. This is consistent with our study results, in which remnant cholesterol can be used as a biomarker to predict kidney outcomes in patients with T2DM and DN.

Previous studies have indicated that remnant cholesterol is an independent predictor of new-onset diabetes in the general population and kidney transplant recipients [ 18 , 19 , 20 ]. One of these studies found that the association between remnant cholesterol and new-onset diabetes may be mediated through insulin resistance and pro-inflammatory status [ 18 ]. Ohnishi et al. and Funada et al. reported the correlation between remnant cholesterol and insulin resistance [ 21 , 22 ]. Moreover, the association between insulin resistance and the progression of DN has been reported in many clinical studies [ 23 , 24 , 25 ]. Numerous in vivo and in vitro experiments [ 26 ] have demonstrated that the pathophysiology of insulin resistance contributes to renal injury, including insulin resistance, which can contribute to the progression of glomerular hypertension and hyperfiltration by mediating an increase in vascular nitric oxide (NO) and transforming growth factor β1 (TGF-β1), higher salt sensitivity via upregulation of sodium-glucose cotransporters, endothelial dysfunction, and proteinuria via increased adipokine levels, activation of the TGF-β1/TGF-β receptor system and enhancement of profibrotic and pro-oxidant effects in glomerular cells via elevated leptin levels.

In addition, previous studies [ 18 , 27 ] have observed a strong association between high remnant cholesterol and low-grade systemic inflammation, as evidenced by elevated C-reactive protein (CRP) and white blood cells (WBCs), suggesting that high remnant cholesterol is often accompanied by a proinflammatory state. In the Chronic Renal Insufficiency Cohort (CRIC) study [ 28 ], biomarkers of inflammation (IL-1β, IL-1 receptor antagonists, IL-6, TNF-α, CRP, and fibrinogen) were negatively associated with renal function and positively associated with proteinuria. Recently, low-grade chronic inflammation has also been shown to contribute to the progression of diabetic kidney disease, and several inflammatory biomarkers have been reported as prognostic markers to risk-stratify patients for disease progression and all-cause mortality [ 29 ]. However, whether remnant cholesterol contributes to DN progression through the mechanism of insulin resistance and low-grade system inflammation remains to be further investigated.

Furthermore, we found that remnant cholesterol and arteriolar hyalinosis may be related. Arteriolar hyalinosis, a characteristic pathological change in diabetes, has also been suggested as a risk factor for rapid decline in GFR. Due to the sample size limitation and the specificity of the study population, the results need to be validated in a larger diabetic population to explore whether residual cholesterol could have a role in the progression of diabetic nephropathy by affecting renal arteriolar hyalinization.

Moreover, another possible reason for DN progression is the atherogenic effect of remnant cholesterol. Numerous studies have shown that higher remnant cholesterol is associated with a higher risk of cardiovascular events and cardiovascular death in the general population and T2DM patients [ 7 , 8 , 9 , 30 ]. Remnant cholesterol, the cholesterol component of triglyceride-rich lipoproteins (TRLs), is extremely atherogenic. Triglycerides, but not cholesterol, can be degraded in tissues or cells. TRLs cross the arterial wall where triglycerides are degraded and remnant cholesterol is deposited in the arterial wall, which in turn is taken up by macrophages or smooth muscle, generating foam cells and ultimately leading to the formation of atherosclerotic plaques [ 30 ]. Although, there is a common mechanism between microvascular and macrovascular complications of diabetes. Whether this is the reason for the further deterioration of renal function in DN due to remnant cholesterol needs to be further verified.

The results of this study also provide new ideas and perspectives for the lipid management of DN. First, clinicians can assess the risk of progression to ESKD in DN patients based on remnant cholesterol. According to our results, clinicians should pay more attention to patients with remnant cholesterol >1.02 mmol/L and take more aggressive lipid-lowering therapy to slow the progression of DN. Second, according to the recommendations of the 2013 KDIGO Clinical Practice Guidelines for Lipid Management in CKD [ 31 ], clinicians should regularly monitor patients’ triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol and assess patients’ risk of cardiovascular events based on LDL-c levels. Recently, several studies have found that remnant cholesterol may be a better marker than LDL-c for predicting cardiovascular outcomes in patients with T2DM [ 30 ]. Then, attempts should be made to incorporate remnant cholesterol to participate in the lipid management of DN patients to help decrease the incidence of cardiovascular events and death. However, it is worth noting that the optimal value of remnant cholesterol to guide lipid management in DN patients still needs to be determined in more and larger studies.

Up to now, statins are used to lower plasma LDL-c concentrations [ 32 ] and peroxisome proliferator–activated receptor (PPAR) agonizts are used to lower plasma triglyceride (TG) concentrations [ 33 , 34 , 35 ]. However, the use of first generation PPARα agonist (fibrate) has been limited by its side effects, including elevations in serum creatinine and homocysteine. Recently, in a randomized, placebo-controlled, double-blind, parallel-group phase 2 trial [ 36 ] enrolling statin-treated patients with hypertriglyceridemia, it was observed that a novel second-generation PPARα agonist (pemafibrate) is effective, safe, and well-tolerated for the reduction of TG, and also for the reduction of apoB48, apoCIII, and remnant cholesterol concentrations. This provides a new possibility and option to lower plasma triglycerides and remnant cholesterol concentrations. Unfortunately, there are no studies on the effects of pemafibrate on cardiovascular events and kidney outcomes. Therefore, further validation of the heart and kidney benefits necessitates additional real-world studies.

There are also some limitations in this study. First, we did not follow up with the patients’ lipids over time and dynamically and therefore could not observe the relationship between remnant cholesterol variability and the progression of DN to ESKD. Second, the outcomes of this study lacked data on cardiovascular events and deaths, higher RC levels have been shown to be associated with a high risk of cardiovascular and non-cardiovascular deaths, with an unknown association with the risk of cancer death. Third, this is a retrospective cohort study. Thus, selective bias is inevitable. However, given the overall matched baseline clinicopathological variables between the different groups and the use of Cox analysis, the results were generally reliable. Fourth, the sample size was limited, with only 334 patients included. What’s more, as a drug that affects both residual cholesterol and renal prognosis, the use of SGLT2i was not taken into account and may have influenced the analysis results. But considering that the drug was not highly utilized in China at that time, it had little impact on the reliability of the results. Finally, the results may be only applicable to patients with T2DM and biopsy-proven DN, not to patients with DKD or diabetes, and CKD.

In conclusion, this longitudinal cohort study highlights the role of remnant cholesterol in patients with T2DM and biopsy-proven DN, extending previous knowledge. We showed that by calculating remnant cholesterol from standard lipid profiles, the progression of DN can be predicted independently of several clinically meaningful risk factors. The increasing burden of diabetes and its complications is concerning, and therefore, an urgent need for more efficient treatment strategies exists. Whether lowering remnant cholesterol could translate into a reduction in microvascular complications of diabetes remains to be clarified, and for that purpose, it needs to be assessed whether the associations we present in this observational study are causal or not.

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These authors contributed equally: Yuancheng Zhao, Ke Liu, Yutong Zou

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Department of Nephrology, West China Hospital of Sichuan University, Chengdu, 610041, China

Yuancheng Zhao, Ke Liu, Yutong Zou, Yucheng Wu, Jia Yang, Xiang Xiao, Xuegui Ju, Qin Yang, Yanlin Lang & Fang Liu

Laboratory of Diabetic Kidney Disease, Kidney Research Institute, Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China

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F. Liu and Y. Zhao designed the experiments. Data collection and analysis were performed by K. Liu, Y. Zou, Y. Wu, J. Yang, X. Xiao, X. Ju, Q. Yang, Y. Lang, and K. Liu. Y. Zhao, K. Liu, and Y. Zou wrote the manuscript, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Zhao, Y., Liu, K., Zou, Y. et al. Remnant cholesterol and the risk of diabetic nephropathy progression to end-stage kidney disease in patients with type 2 diabetes mellitus: a longitudinal cohort study. Endocrine (2024). https://doi.org/10.1007/s12020-024-03948-4

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DOI : https://doi.org/10.1007/s12020-024-03948-4

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Researchers find type 2 diabetes cases more than doubled seven decades after exposure to famine

by Columbia University's Mailman School of Public Health

The long-lasting impact of war on global diabetes prevalence

Researchers at Columbia University Mailman School of Public Health, the University of North Carolina at Chapel Hill and at the National Academy of Sciences of Ukraine used the setting of the man-made Ukrainian Holodomor famine of 1932–1933 to examine the relation between prenatal famine and adult type 2 diabetes mellitus (T2DM).

They studied 128,225 type 2 diabetes cases diagnosed between 2000–2008 among 10,186,016 male and female Ukrainians born between 1930 and 1938.

Individuals who were exposed in early gestation to the famine had a more than two-fold likelihood of developing type 2 diabetes compared to those unexposed to the famine, according to a study led by Columbia University Mailman School of Public Health. The results are published in the journal Science .

The famine led to 4 million excess deaths in the short-term and losses were concentrated in a six-month period. The Holodomor far exceeded other famines in terms of its intensity. Life expectancies at birth in 1933 were only 7.2 years for females and 4.3 for males.

"The Ukraine setting provided an unusual opportunity to investigate the long-term impact of the Holodomor—or death by hunger—on type 2 Diabetes Mellitus cases diagnosed seven decades after prenatal famine exposure," said L.H. Lumey, MD, professor of Epidemiology at Columbia Public Health.

"With the famine concentrated in a six-month period in early 1933, we are able to pinpoint the timing of famine together with extreme variations in intensity across provinces."

This concentration was the result of Stalin's use of famine as a weapon of terror against Ukrainian farmers. When Ukraine could not fulfill its grain procurement quotas to the Soviet Central Government, having not enough for themselves, drastic measures were implemented to fulfill the quotas, under the excuse that counter-revolutionary elements sabotaged grain procurement.

A countrywide campaign of searches of peasants' homes looking for "hidden" or "stolen" grain was launched in late 1932 and expanded in early 1933. All or most of the food was confiscated during many of these searches, leaving families without any food for the rest of the winter. In addition, measures were implemented that curtailed Ukrainian peasants' travel in search of food.

These measures created a perfect storm. Many rural families were left without any food; avenues to search for food were closed and grain reserve funds were depleted.

Thousands of rural families were condemned to a slow death by starvation in their villages. The result was an extraordinary increase in Holodomor excess deaths between January and June 1933.

At the peak of the famine in June 1933, there were, on average, 28,000 famine-related deaths per day caused by the famine, equivalent to 1,167 deaths per hour or 19 per minute.

"Our study into the long-term health impact of the Holodomor famine offers several critical lessons for addressing health challenges posed by national disasters," observes Lumey.

"It underscores the necessity for a comprehensive health care and policy framework that takes into account the lasting effects of early-life adversities on population health and their potential long-term repercussions on chronic diseases and mental health ."

While individuals diagnosed with T2DM in 2000–2008 may also be overweight or obese and have other risk factors for the disease, the relation between adult T2DM risk and the place and date of birth at the time of the famine is so specific that famine exposure in early gestation appears to be the dominant factor that overrides all others, according to the research team.

"This awareness should prompt a proactive approach among policymakers and public health officials to anticipate the increased health care needs among populations affected by national disasters. It also highlights the importance of raising awareness about the potential long-term health effects of early-life adversities," observed Lumey.

"Besides the need to develop policies for addressing long-term health challenges after a national disaster, the results of our study underscore the importance of policies aimed at preventing events like the Holodomor from happening again. Russia's invasion of Ukraine in 2022 shows that history repeats itself," points out Dr. Wolowyna of the University of North Carolina at Chapel Hill.

"The three-month siege in 2022 of the city of Mariupol during the current war in Ukraine to starve the population into surrender serves as a reminder of a current and real danger. The blockade of Ukrainian ports to prevent the export of Ukrainian grain to developing countries in Africa and Asia, has increased the danger of starvation for millions of persons in these countries."

Peter Klimek, The lasting effects of famine, Science (2024). DOI: 10.1126/science.adr1425 . www.science.org/doi/10.1126/science.adr1425

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Diabetes Spectr
v.29(1); 2016 Feb

Case Study: Remission of Type 2 Diabetes After Outpatient Basal Insulin Therapy

Sierra c. schmidt.

1 Auburn University Harrison School of Pharmacy, Auburn, AL

Martha Ann Huey

Heather p. whitley.

2 Baptist Health System, Montgomery Family Medicine Residency Program, Montgomery, AL

Diabetes is a chronic, progressive disease with potentially serious sequelae. Treatment for type 2 diabetes often begins with oral agents and eventually requires insulin therapy. As the disease progresses, drug therapies are often intensified and rarely reduced to control glycemia. Conversely, in type 1 diabetes, some patients experience a “honeymoon period” shortly after diagnosis, wherein insulin needs decrease significantly before intensification is needed ( 1 ). No comparable honeymoon period has been widely described for type 2 diabetes. However, a few studies have demonstrated that drug-free glycemic control can be achieved in type 2 diabetes for 12 months on average after a 2-week continuous insulin infusion ( 2 – 4 ). Here, we describe an unusual case of a 26-month drug holiday induced with outpatient basal insulin in a patient newly diagnosed with type 2 diabetes.

Case Presentation

A 69-year-old white woman (weight 72.7 kg, height 59 inches, BMI 32.3 kg/m 2 ) was diagnosed with type 2 diabetes in June 2011. She presented with an A1C of 17.6% (target <7%) and a fasting blood glucose (FBG) of 452 mg/dL (target 70–130 mg/dL). Before diagnosis, the patient had not used any oral or parenteral steroids nor had she experienced any traumatic physical or emotional event or illness that could have abruptly increased her blood glucose. Metformin 500 mg twice daily was initiated at diagnosis, but was discontinued 9 days later to avoid risk of lactic acidosis, as her serum creatinine was 1.5 mg/dL. At that time, her fasting self-monitoring of blood glucose (SMBG) values ranged from 185 to 337 mg/dL. Treatment with 25 units of insulin detemir daily (0.34 units/kg/day) was initiated in place of metformin. The patient was counseled on diet modifications and encouraged to exercise.

One month later (July 2011), the patient’s fasting SMBG values had improved to a range of 71–212 mg/dL with a single hypoglycemic episode (58 mg/dL); her weight and BMI increased slightly to 74.1 kg and 32.9 kg/m 2 , respectively. Hypoglycemia education was reinforced, and insulin therapy was switched from 25 units of detemir delivered with the Levemir FlexPen to 28 units (0.38 units/kg/day) of insulin glargine delivered with the Lantus SoloStar due to the patient’s preference for this device. Two weeks later, the patient reported continued improvements in fasting SMBG (70–175 mg/dL) with one hypoglycemic episode (67 mg/dL). In response to the hypoglycemic episode, her insulin glargine dose was decreased to 25 units daily.

In September, the patient reported fasting SMBG values ranging between 71 and 149 mg/dL, and her A1C was 7.9%. On days when the patient skipped lunch, her midday blood glucose level would drop to <70 mg/dL (54–60 mg/dL). She was counseled not to skip meals, and her insulin glargine dose was maintained.

In October, the patient’s weight was 71.4 kg, and her BMI was 31.7 kg/m 2 . She reported recently initiating a cinnamon supplement and switching her beverage intake from sugar-sweetened products to water and diet soda. Although the majority of her fasting SMBG values were controlled (80–110 mg/dL), she had experienced six hypoglycemic episodes (FBG 13–64 mg/dL). All values were objectively confirmed in the patient’s glucose meter, and the meter was replaced in case of device error. Her daily insulin glargine dose was decreased to 20 units (0.28 units/kg/day).

In December, her SMBG values ranged between 70 and 106 mg/dL preprandially and 111 and 207 mg/dL postprandially, and she had had six additional hypoglycemic episodes (42–66 mg/dL). The patient’s weight remained stable at 71.4 kg (BMI 31.7 kg/m 2 ). At this follow-up visit, her daily insulin glargine dose was decreased further to 15 units (0.21 units/kg/day).

The patient self-discontinued daily insulin glargine in March 2012 but continued using the cinnamon supplements. She continued to perform SMBG 1–3 times/day, anticipating loss of glycemic control. During the next 2 years, her A1C remained stable (from 6.3% in January 2012 to 6.9% in May 2014) ( Figure 1 ).

An external file that holds a picture, illustration, etc.
Object name is 50fig1.jpg

Daily basal insulin dose and A1C over time. Black triangle = insulin units; black square = A1C.

At a follow-up visit in May 2014, the patient’s SMBG indicated a need for resumed drug therapy (FBG 107–169 mg/dL, postprandial blood glucose 108–328 mg/dL). Her weight at this time was 65.5 kg (BMI 29.1 kg/m 2 ). Insulin glargine was reinitiated at 5 units daily (0.08 units/kg/day).

During the drug-free period of March 2012 to May 2014, the patient maintained her lack of sugar-sweetened beverage consumption. However, she reported having difficulties purchasing healthy food options because of financial constraints. In August 2013, she was specifically encouraged to incorporate physical activity (walking) into her daily routine. The patient’s weight during the drug-free interval declined from 70 kg in March 2012 to 65.5 kg in May 2014.

Hyperglycemia causes pancreatic β-cell toxicity, leading to decreased insulin release ( 3 ). In type 1 diabetes, the honeymoon period occurs when residual pancreatic β-cell function is partially restored for an average of 7.2 months, as hyperglycemic stress is removed before the β-cells are ultimately destroyed ( 1 , 3 ).

Past studies demonstrated induction of a drug-free period when patients newly diagnosed with type 2 diabetes were treated with 2–3 weeks of intensive insulin therapy ( 2 – 5 ). Ilkova et al. ( 2 ) induced a 12-month drug-free period in 46.2% ( n = 6) of patients using an insulin infusion averaging 0.61 units/kg/day. Three patients maintained glycemic control for 37–59 months. Li et al. ( 3 ) also induced a 12-month drug-free period in 47.1% ( n = 32) of patients with an insulin infusion of 0.7 units/kg. Additional studies indicate that basal-bolus insulin therapy (0.37–0.74 units/kg/day) using NPH and regular insulin can also induce a 12-month drug-free period in a similar percentage of patients (43.8–44.9%) ( 4 , 5 ).

The mechanism of remission appears to be related to resumption of endogenous insulin production after glucotoxicity is resolved. Glucotoxicity has been shown to inhibit first-phase insulin secretion from the pancreatic β-cells ( 3 ). Li et al. ( 3 ) theorized that an insulin infusion corrects hyperglycemia and removes stress from the β-cells, allowing them to produce insulin, resulting in euglycemia. Their study quantified an increase in secretion of endogenous insulin (44%) and C-peptide (26%) after 2 weeks of continuous insulin infusion. The mechanism through which insulin induces a period of drug-free glycemic control in type 2 diabetes appears to be similar to that causing the honeymoon period in type 1 diabetes.

To our knowledge, this is the first report of basal insulin monotherapy–induced remission of type 2 diabetes. Previous studies required multiple daily injections in a basal-bolus therapy regimen using NPH and regular insulin or hospitalization of patients administered a continuous insulin infusion ( 2 – 5 ).

Basal-only insulin therapy may be a slower method of achieving remission compared to more intensive insulin regimens. In this case, basal insulin was maintained for 9 months. However, according to the FBG trend, discontinuation could have occurred sooner. This report suggests that a trial of basal insulin dosed at 0.2–0.3 units/kg/day, with follow-up every 2–4 weeks in severely hyperglycemic patients with newly diagnosed type 2 diabetes, may be an alternative method to achieving temporary remission. Although this insulin regimen requires a longer timeframe compared to remission induced by basal-bolus therapy or continuous insulin infusion, it provides a more convenient outpatient therapeutic option at a lower cost.

Limitations of this case study include the patient’s use of cinnamon supplementation, which was continued throughout the drug-free period. Although reports are conflicting regarding its efficacy in type 2 diabetes, it is possible that cinnamon may have exerted a mild antidiabetic effect. Positive cinnamon studies have demonstrated a 0.36% A1C reduction after 3 months of use ( 6 ). Additionally, the patient’s weight declined by 3.75% during the 9 months of basal insulin therapy, which was likely in response to introducing dietary modifications related to beverage consumption. Most studies suggest that an A1C reduction of 0.36% ( 7 ) to 0.66% ( 8 ) can be achieved with intensive lifestyle interventions. Therefore, it is unlikely that cinnamon in combination with the mild lifestyle modifications accounted for a nearly 11% A1C reduction from baseline.

Eliminating the consumption of sugar-rich beverages alters the postprandial glycemic curve. In clinical practice, suppressing postprandial blood glucose excursions by adopting significant dietary improvements may postpone or obviate the need for bolus insulin therapy. Likewise, the remission of diabetes potentially may be achieved, as seen in this case, with monotherapy basal insulin when dietary modifications significantly alter the postprandial glycemic curve. However, it is unknown whether remission can be achieved using basal insulin administration alone in patients who choose not to incorporate lifestyle modifications or in patients with baseline healthy eating and exercise habits.

Although weight changes did not appear to contribute to disease remission, the moderate weight loss (6.5%) achieved during the drug-free interval and continued SMBG both may have contributed to maintaining and extending the remission period. The Diabetes Prevention Program ( 9 ) showed that lifestyle modifications aimed at achieving a 7% reduction of weight significantly delay the onset of diabetes compared to placebo and metformin. Finally, performing SMBG through the drug-free period may have empowered the patient by providing objective criteria necessary to validate the benefits of lifestyle modifications.

Based on this case, it is possible that initial type 2 diabetes management with basal insulin can temporarily restore β-cell function to a degree to which blood glucose control can be maintained without drug therapy. Although previous studies conducted with intensive insulin regimens have reported response rates nearing 50% for ∼12 months ( 2 – 5 ), future studies should investigate the ideal basal dose, percentage of patient responders, duration of drug-free glycemic control, and mechanism through which this phenomenon occurs. This case further highlights the need to educate every newly diagnosed patient about the treatment of hypoglycemic events.

The purposeful remission of diabetes is not widely attempted or generally considered possible. Although literature exists regarding the temporary honeymoon period experienced after insulin initiation in some people with type 1 diabetes ( 1 ), comparatively little research is available regarding the influence of insulin on the remission of type 2 diabetes. Current literature suggests benefit in nearly 50% of patients newly diagnosed with type 2 diabetes using one of the following strategies: a 2-week inpatient insulin infusion or multiple daily injections of basal-bolus therapy ( 2 – 5 ). However, there are disadvantages to these methods. A continuous insulin infusion requires inpatient admission, whereas a basal-bolus insulin regimen requires purchase of two products and administration of multiple subcutaneous injections daily. Unfortunately, both methods may be impractical, costly, and inconvenient for many patients newly diagnosed with type 2 diabetes.

This case outlines a third potential option for inducing remission of type 2 diabetes: basal insulin monotherapy. Using this approach avoids the costly and inconvenient hospital admission required for the continuous insulin infusion strategy. Furthermore, the cost of drug therapy is reduced with the purchase of one rather than two insulin products, as needed in a basal-bolus insulin regimen. Additionally, using basal insulin alone reduces the risk of hypoglycemic events that may occur with stacking of multiple insulin products. Finally, requiring only one injection of insulin each day offers a more manageable alternative for newly diagnosed patients compared to the multiple daily injections required with a basal-bolus insulin regimen.

By using this basal insulin strategy, the patient in this case was able to achieve drug-free glycemic control for 26 months. Early initiation of basal insulin monotherapy in patients newly diagnosed with type 2 diabetes is a more convenient and cost-effective approach than methods previously described and could potentially induce remission of type 2 diabetes in other patients.

Duality of Interest

No potential conflicts of interest relevant to this article were reported.

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25-hydroxyvitamin d, vitamin d binding protein and gestational diabetes mellitus: a two-sample mendelian randomization study.

1. Introduction

2.1. study design, 2.2. data sources, 2.3. genetic variant selection, 2.4. mr analysis, 3.1. causal relationship between 25(oh)d and gdm, 3.2. causal relationship between vdbp and gdm, 4. discussion, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement.

https://gwas.mrcieu.ac.uk/datasets/ukb-d-30890_irnt/
https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90000618/
https://gwas.mrcieu.ac.uk/datasets/ieu-b-4808/
https://gwas.mrcieu.ac.uk/datasets/prot-a-1179/
https://gwas.mrcieu.ac.uk/datasets/finn-b-GEST_DIABETES/

Acknowledgments

Conflicts of interest.

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Click here to enlarge figure

Trait	Number of Cases	Number of Controls	Sample Size	Data Source	Population	Year	ID	Fmin
Exposure
Vitamin D	NA	NA	449,835	UKB	European	2018	ukb-d-30890_irnt	29.67
Serum 25(OH)D	NA	NA	496,946	EBI	European	2020	ebi-a-GCST90000618	30.46
25(OH)D	NA	NA	441,291	IEU	European	2020	ieu-b-4808	21.00
Vitamin D Binding Protein	NA	NA	3301	INTERVAL	European	2018	prot-a-1179	22.28
Outcome
GDM	5687	117,892	123,579	FinnGen	European	2021	finn-b-GEST_DIABETES	/

Exposure	Method	SNPs	OR (95% CI)	p
25(OH)D	IVW	111	0.71 (0.50, 0.99)	0.046
	MR Egger	111	0.61 (0.34, 1.10)	0.103
	Maximum likelihood	111	0.70 (0.52, 0.95)	0.022
	Weighted median	111	0.72 (0.43, 1.20)	0.210
	Weighted mode	111	0.80 (0.52, 1.24)	0.314
25(OH)D (IVs independent of BMI)	IVW	90	0.76 (0.55, 1.06)	0.101
	MR Egger	90	0.66 (0.38, 1.13)	0.135
	Maximum likelihood	90	0.76 (0.55, 1.04)	0.090
	Weighted median	90	0.72 (0.43, 1.20)	0.193
	Weighted mode	90	0.77 (0.49, 1.22)	0.233

Exposure	Heterogeneity Test				Pleiotropy Test
	IVW		MR–Egger		MR–Egger Intercept			MR–PRESSO Results (p)
	Q	p	Q	p	Intercept	SE	p	Raw	Outlier-Corrected
25(OH)D	142.35	0.021	141.87	0.019	0.003	0.005	0.5465	0.0874	0.1691
25(OH)D (IVs independent of BMI)	95.01	0.312	94.54	0.298	0.003	0.005	0.5108	0.5092	NA

Exposure	Method	SNPs	OR (95% CI)	p
VDBP	IVW	11	0.98 (0.93, 1.03)	0.408
	MR Egger	11	0.98 (0.91, 1.06)	0.680
	Maximum likelihood	11	0.98 (0.93, 1.03)	0.405
	Weighted median	11	0.98 (0.93, 1.04)	0.545
	Weighted mode	11	0.98 (0.93, 1.03)	0.473
VDBP (IVs independent of BMI)	IVW	9	0.97 (0.92, 1.02)	0.243
	MR Egger	9	0.99 (0.92, 1.06)	0.730
	Maximum likelihood	9	0.97 (0.92, 1.02)	0.248
	Weighted median	9	0.98 (0.93, 1.04)	0.527
	Weighted mode	9	0.98 (0.93, 1.03)	0.457

Exposure	Heterogeneity Test				Pleiotropy Test
	IVW		MR–Egger		MR–Egger Intercept			MR–PRESSO Results (p)
	Q	p	Q	p	Intercept	SE	p	Raw	Outlier-Corrected
VDBP	9.23	0.419	9.23	0.511	−0.003	0.015	0.8606	0.4095	NA
VDBP (IVs independent of BMI)	5.88	0.661	5.46	0.603	−0.010	0.016	0.5400	0.2103	NA

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Qiu, Y.; Ainiwan, D.; Huang, Y.; Zhang, L.; Cheng, H.; Alifu, X.; Zhou, H.; Xv, N.; Wang, B.; Wang, S.; et al. 25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study. Nutrients 2024 , 16 , 2603. https://doi.org/10.3390/nu16162603

Qiu Y, Ainiwan D, Huang Y, Zhang L, Cheng H, Alifu X, Zhou H, Xv N, Wang B, Wang S, et al. 25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study. Nutrients . 2024; 16(16):2603. https://doi.org/10.3390/nu16162603

Qiu, Yiwen, Diliyaer Ainiwan, Ye Huang, Libi Zhang, Haoyue Cheng, Xialidan Alifu, Haibo Zhou, Nuo Xv, Boya Wang, Shuhui Wang, and et al. 2024. "25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study" Nutrients 16, no. 16: 2603. https://doi.org/10.3390/nu16162603

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Clinical pearls, case study: treating hypertension in patients with diabetes.

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Evan M. Benjamin; Case Study: Treating Hypertension in Patients With Diabetes. Clin Diabetes 1 July 2004; 22 (3): 137–138. https://doi.org/10.2337/diaclin.22.3.137

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L.N. is a 49-year-old white woman with a history of type 2 diabetes,obesity, hypertension, and migraine headaches. The patient was diagnosed with type 2 diabetes 9 years ago when she presented with mild polyuria and polydipsia. L.N. is 5′4″ and has always been on the large side,with her weight fluctuating between 165 and 185 lb.

Initial treatment for her diabetes consisted of an oral sulfonylurea with the rapid addition of metformin. Her diabetes has been under fair control with a most recent hemoglobin A 1c of 7.4%.

Hypertension was diagnosed 5 years ago when blood pressure (BP) measured in the office was noted to be consistently elevated in the range of 160/90 mmHg on three occasions. L.N. was initially treated with lisinopril, starting at 10 mg daily and increasing to 20 mg daily, yet her BP control has fluctuated.

One year ago, microalbuminuria was detected on an annual urine screen, with 1,943 mg/dl of microalbumin identified on a spot urine sample. L.N. comes into the office today for her usual follow-up visit for diabetes. Physical examination reveals an obese woman with a BP of 154/86 mmHg and a pulse of 78 bpm.

What are the effects of controlling BP in people with diabetes?

What is the target BP for patients with diabetes and hypertension?

Which antihypertensive agents are recommended for patients with diabetes?

Diabetes mellitus is a major risk factor for cardiovascular disease (CVD). Approximately two-thirds of people with diabetes die from complications of CVD. Nearly half of middle-aged people with diabetes have evidence of coronary artery disease (CAD), compared with only one-fourth of people without diabetes in similar populations.

Patients with diabetes are prone to a number of cardiovascular risk factors beyond hyperglycemia. These risk factors, including hypertension,dyslipidemia, and a sedentary lifestyle, are particularly prevalent among patients with diabetes. To reduce the mortality and morbidity from CVD among patients with diabetes, aggressive treatment of glycemic control as well as other cardiovascular risk factors must be initiated.

Studies that have compared antihypertensive treatment in patients with diabetes versus placebo have shown reduced cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS), which followed patients with diabetes for an average of 8.5 years, found that patients with tight BP control (< 150/< 85 mmHg) versus less tight control (< 180/< 105 mmHg) had lower rates of myocardial infarction (MI), stroke, and peripheral vascular events. In the UKPDS, each 10-mmHg decrease in mean systolic BP was associated with a 12% reduction in risk for any complication related to diabetes, a 15% reduction for death related to diabetes, and an 11% reduction for MI. Another trial followed patients for 2 years and compared calcium-channel blockers and angiotensin-converting enzyme (ACE) inhibitors,with or without hydrochlorothiazide against placebo and found a significant reduction in acute MI, congestive heart failure, and sudden cardiac death in the intervention group compared to placebo.

The Hypertension Optimal Treatment (HOT) trial has shown that patients assigned to lower BP targets have improved outcomes. In the HOT trial,patients who achieved a diastolic BP of < 80 mmHg benefited the most in terms of reduction of cardiovascular events. Other epidemiological studies have shown that BPs > 120/70 mmHg are associated with increased cardiovascular morbidity and mortality in people with diabetes. The American Diabetes Association has recommended a target BP goal of < 130/80 mmHg. Studies have shown that there is no lower threshold value for BP and that the risk of morbidity and mortality will continue to decrease well into the normal range.

Many classes of drugs have been used in numerous trials to treat patients with hypertension. All classes of drugs have been shown to be superior to placebo in terms of reducing morbidity and mortality. Often, numerous agents(three or more) are needed to achieve specific target levels of BP. Use of almost any drug therapy to reduce hypertension in patients with diabetes has been shown to be effective in decreasing cardiovascular risk. Keeping in mind that numerous agents are often required to achieve the target level of BP control, recommending specific agents becomes a not-so-simple task. The literature continues to evolve, and individual patient conditions and preferences also must come into play.

While lowering BP by any means will help to reduce cardiovascular morbidity, there is evidence that may help guide the selection of an antihypertensive regimen. The UKPDS showed no significant differences in outcomes for treatment for hypertension using an ACE inhibitor or aβ-blocker. In addition, both ACE inhibitors and angiotensin II receptor blockers (ARBs) have been shown to slow the development and progression of diabetic nephropathy. In the Heart Outcomes Prevention Evaluation (HOPE)trial, ACE inhibitors were found to have a favorable effect in reducing cardiovascular morbidity and mortality, whereas recent trials have shown a renal protective benefit from both ACE inhibitors and ARBs. ACE inhibitors andβ-blockers seem to be better than dihydropyridine calcium-channel blockers to reduce MI and heart failure. However, trials using dihydropyridine calcium-channel blockers in combination with ACE inhibitors andβ-blockers do not appear to show any increased morbidity or mortality in CVD, as has been implicated in the past for dihydropyridine calcium-channel blockers alone. Recently, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in high-risk hypertensive patients,including those with diabetes, demonstrated that chlorthalidone, a thiazide-type diuretic, was superior to an ACE inhibitor, lisinopril, in preventing one or more forms of CVD.

L.N. is a typical patient with obesity, diabetes, and hypertension. Her BP control can be improved. To achieve the target BP goal of < 130/80 mmHg, it may be necessary to maximize the dose of the ACE inhibitor and to add a second and perhaps even a third agent.

Diuretics have been shown to have synergistic effects with ACE inhibitors,and one could be added. Because L.N. has migraine headaches as well as diabetic nephropathy, it may be necessary to individualize her treatment. Adding a β-blocker to the ACE inhibitor will certainly help lower her BP and is associated with good evidence to reduce cardiovascular morbidity. Theβ-blocker may also help to reduce the burden caused by her migraine headaches. Because of the presence of microalbuminuria, the combination of ARBs and ACE inhibitors could also be considered to help reduce BP as well as retard the progression of diabetic nephropathy. Overall, more aggressive treatment to control L.N.'s hypertension will be necessary. Information obtained from recent trials and emerging new pharmacological agents now make it easier to achieve BP control targets.

Hypertension is a risk factor for cardiovascular complications of diabetes.

Clinical trials demonstrate that drug therapy versus placebo will reduce cardiovascular events when treating patients with hypertension and diabetes.

A target BP goal of < 130/80 mmHg is recommended.

Pharmacological therapy needs to be individualized to fit patients'needs.

ACE inhibitors, ARBs, diuretics, and β-blockers have all been documented to be effective pharmacological treatment.

Combinations of drugs are often necessary to achieve target levels of BP control.

ACE inhibitors and ARBs are agents best suited to retard progression of nephropathy.

Evan M. Benjamin, MD, FACP, is an assistant professor of medicine and Vice President of Healthcare Quality at Baystate Medical Center in Springfield, Mass.

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DM-II, Case study
Pathophysiology of type 2 diabetes mellitus
Case Studies of Patients with Type 2 Diabetes Mellitus: Exercises in
A Case Study on Type 2 Diabetes Mellitus
Diabetes Mellitus Case Study
(PDF) Type 2 Diabetes Mellitus (Case Study at Insan Rizkillah Clinic)

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Case Study: A Patient With Uncontrolled Type 2 Diabetes and Complex
In diabetes, the role of advanced practice nurses has significantly contributed to improved outcomes in the management of type 2 diabetes,5 in specialized diabetes foot care programs,6 in the management of diabetes in pregnancy,7 and in the care of pediatric type 1 diabetic patients and their parents.8,9 Furthermore, NPs have also been ...
Case 6-2020: A 34-Year-Old Woman with Hyperglycemia
The patient received a diagnosis of type 2 diabetes mellitus; lifestyle modification was recommended. Three months post partum, the glycated hemoglobin level was 5.9% and the BMI was 30.0. ... observational case control studies. PLoS One 2013; 8 (6): e65326. [PMC free article] [Google Scholar] 34. The HAPO Study Cooperative Research Group.
Case Study: A Woman With Type 2 Diabetes and Severe
In type 2 diabetes, characterized by insulin resistance and insulin deficiency, the pathophysiology of hypertriglyceridemia is an increased hepatic production of triglycerides as well as a decreased lipoprotein lipase activity leading to slower breakdown of VLDL cholesterol and chylomicrons.3 The American Diabetes Association (ADA) Clinical ...
Interactive diabetes case 17: A 47-year-old patient with newly
CASE. A 47-year-old woman was found to have hyperglycemia at a health fair when a random blood glucose level was 227 mg/dL (12.6 mmol/L). Several days later, a fasting blood glucose value was 147 mg/dL (8.2 mmol/L). She has no previous history of diabetes, is alarmed by the possibility of having this disorder, and seeks your advice.
Case Studies of Patients with Type 2 Diabetes Mellitus ...
Diabetes mellitus currently affects 6.4% or 285 million adults worldwide, and that number is expected to increase to 7.7% or 439 million by 2030. 1 In the United States, the prevalence of diabetes in adults increased from 11.3% in 2010 to 12.3% in 2012. 2 The current type 2 diabetes mellitus (T2DM) epidemic is closely associated with a parallel obesity epidemic, with more than 85% of patients ...
Case 10-2024: A 46-Year-Old Woman with Hyperglycemia Refractory to
A 46-year-old woman with type 2 diabetes was admitted to this hospital because of hyperglycemia for which she was receiving over 2000 units of insulin per day. A diagnosis was made.
Two Cases of Successful Type 2 Diabetes Control with Lifestyle
A recent study reported that oral medication was eventually needed to control hyperglycemia in patients with diabetes refractory to management with proper lifestyle modification.12 However, lifestyle modification is important, and is a cornerstone in the treatment of diabetes, and it should be a mandatory treatment for type 2 diabetes.
Type 2 diabetes: a case study
This article examines the aetiology, pathophysiology, diagnosis and treatment of type 2 diabetes using a case study approach. The psychosocial implications for the patient are also discussed. The case study is based on a patient with diabetes who was admitted to hospital following a hypoglycaemic episode and cared for during a practice placement.
Nutrient patterns and risk of diabetes mellitus type 2: a case-control
Study population. This study utilized a case-control design and involved participants between the ages of 18 and 60 who had been diagnosed with type 2 diabetes within the previous six months based on specific glucose level criteria (FBS levels of ≥ 126 mg/dl and 2 h-PG levels of ≥ 200 mg/dl []).Healthy individuals within the same age range were also included, with specific glucose level ...
Case Study: A Patient With Type 2 Diabetes Working With an Advanced
B.L. is a 58-year-old white woman who has been referred to the pharmacist clinician for pharmacotherapy assessment and diabetes management. Her multiple medical conditions include type 2 diabetes diagnosed in 1995, hypertension, hyperlipidemia, asthma, coronary artery disease, persistent peripheral edema, and longstanding musculoskeletal pain secondary to a motor vehicle accident.
Nutrient patterns and risk of diabetes mellitus type 2: a case-control
A case-control study was conducted at the Tabriz Center of Metabolism and Endocrinology to investigate the relationship between nutrient patterns and type 2 diabetes (T2D). The study enrolled 225 newly diagnosed cases of T2D and 225 controls. The dietary intake of nutrients was assessed using a validated semi-quantitative food frequency ...
Interactive case study: Making a diagnosis of type 2 diabetes
The new series of case studies from Diabetes & Primary Care is aimed at GPs, practice nurses and other professionals in primary and community care who would like to broaden their understanding of type 2 diabetes. This third case offering provides three mini-case studies that take you through the criteria for making an accurate diagnosis of diabetes and non-diabetic hyperglycaemia.
Case 6-2020: A 34-Year-Old Woman with Hyperglycemia
The patient received a diagnosis of type 2 diabetes mellitus; lifestyle modification was recommended. Three months post partum, the glycated hemoglobin level was 5.9% and the BMI was 30.0 ...
CC, History, and PE
Yazzie's mother had type 2 diabetes mellitus and well-controlled hypertension. Ms. Yazzie's sister died at age 64, the specific cause is unknown. She had been diagnosed with obesity, hypertension, diabetes, and suspected coronary artery disease. Ms. Yazzie's other sister is alive at age 59. She was diagnosed with obesity at age 37 and ...
Diagnosis and Treatment
Treatment. Treatment of type 2 diabetes mellitus (T2DM) focuses on decreasing blood glucose, increasing insulin secretion, or countering insulin resistance. Treatment of symptoms, such as diabetic retinopathy, nephropathy, or neuropathy requires additional and involved patient education, medications, and therapies.
(PDF) Diabetes Mellitus: A Case Study
Diabetes Mellitus: A Case Study . Ain Q and Sadeeqa S* ... Type 2 diabetes mellitus is a state when pancreas unable to make sufficient insulin and results in lack of insulin production.
Putting Theory Into Practice: A Case Study of Diabetes-Related
Tuomilehto J, Lindstrom J, Ericksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New England Journal of Medicine. 2001; 344:1343-1350. [Google Scholar] U. S. Department of Health and Human Services, Medicare Learning Network.
Case Study: Diabetic Ketoacidosis in Type 2 Diabetes: "Look Under the
A recent study evaluating 138 consecutive admissions for DKA at a large academic center observed that 21.7% had type 2 diabetes. 6 Nearly 70% of the admissions involved discontinuation of medications, and almost half had an identifiable infection when an intensive search was undertaken.
[PDF] Case Study: A Patient With Uncontrolled Type 2 Diabetes and
The specialized role of nursing in the care and education of people with diabetes has been in existence for more than 30 years and the emergence and subsequent growth of advanced practice in nursing during the past 20 years has expanded the direct care component, incorporating aspects of both nursing and medical care while maintaining the teaching and counseling roles. The specialized role of ...
Severe Hypertriglyceridemia in Patients with Type 2 Diabetes Mellitus
Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the ...
Development and acceptability of a gestational diabetes mellitus
Assaf-Balut C, García De La Torre N, Duran A, et al. A Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios improves pregnancy outcomes in women without gestational diabetes mellitus: a sub-analysis of the St. Carlos Gestational diabetes mellitus prevention study. Ann Nutr Metab 2019; 74: 69-79.
Determinants of hypertension among diabetic patients in southern
Being overweight and obese, lack of moderate-intensity exercise, age, type 2 diabetes mellitus, duration of Diabetes ≥ 6 years, presence of diabetic nephropathy, and being urban residents were significant determinants of hypertension among diabetic patients. ... Methods: Facility-based unmatched case-control study design was conducted from ...
Case Study: A 30-Year-Old Man With Metformin-Treated Newly Diagnosed
M.P. is a 30-year-old man who was diagnosed with type 2 diabetes 2 weeks before admission to the hospital. He has a strong family history of type 2 diabetes. He smokes heavily (> 20 cigarettes/day) and admits to some alcohol consumption. His primary care physician had started him on metformin,500 mg three times daily.
Remnant cholesterol and the risk of diabetic nephropathy ...
Aim Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease (ESKD). Remnant cholesterol has been investigated as a predictor for the progression of DN in type 1 diabetes mellitus patients, as well as the incidence of DN in type 2 diabetes mellitus (T2DM) patients. This study aimed to evaluate the longitudinal relationship between baseline remnant cholesterol and kidney ...
Researchers find type 2 diabetes cases more than doubled seven decades
They studied 128,225 type 2 diabetes cases diagnosed between 2000-2008 among 10,186,016 male and female Ukrainians born between 1930 and 1938.
Case Study: Remission of Type 2 Diabetes After Outpatient Basal Insulin
However, a few studies have demonstrated that drug-free glycemic control can be achieved in type 2 diabetes for 12 months on average after a 2-week continuous insulin infusion ( 2 - 4 ). Here, we describe an unusual case of a 26-month drug holiday induced with outpatient basal insulin in a patient newly diagnosed with type 2 diabetes.
Case Study: Uncontrolled Type 2 Diabetes in a 48-Year-Old Woman on
M.W. is a 48-year-old woman with a 15-year history of type 2 diabetes that has been treated with insulin for 13 years. ... Case Study: Uncontrolled Type 2 Diabetes in a 48-Year-Old Woman on Interferon β-1b Treatment for Multiple Sclerosis ... Kure M, Sarashina G, Watanabe T, Katsura Y, Nemoto Y, Noritake M, Matsuoka T: Type 1 diabetes mellitus ...
25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes
Background: Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials. Objective: Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association ...
Case Study: Treating Hypertension in Patients With Diabetes
L.N. is a 49-year-old white woman with a history of type 2 diabetes,obesity, hypertension, and migraine headaches. The patient was diagnosed with type 2 diabetes 9 years ago when she presented with mild polyuria and polydipsia. L.N. is 5′4″ and has always been on the large side,with her weight fluctuating between 165 and 185 lb.

Nutrient patterns and risk of diabetes mellitus type 2: a case-control study

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BMC Endocrine Disorders

Interactive case study: Making a diagnosis of type 2 diabetes

Diabetes Distilled: Diabetes-related foot ulcers – detailed advice for primary care

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Diagnosis and Treatment

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Diabetes Mellitus: A Case Study

Case Study: A Patient With Uncontrolled Type 2 Diabetes and Complex Comorbidities Whose Diabetes Care Is Managed by an Advanced Practice Nurse

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Determinants of hypertension among diabetic patients in southern Ethiopia: a case-control study

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Remnant cholesterol and the risk of diabetic nephropathy progression to end-stage kidney disease in patients with type 2 diabetes mellitus: a longitudinal cohort study

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