Phenotypic clusters of type 2 diabetes mellitus among North Indians reveal higher levels of insulin deficiency along with insulin resistance.

BACKGROUND: Type 2 diabetes is now considered a heterogenous disease. Distinct clusters have been identified with patterns varying between Europeans and South Asians as well as between South Indians who have described a novel cluster; Combined Insulin-Resistant and Deficient Diabetes, and individuals from West and East India who have reported that insulin deficiency is the primary driver of heterogeneity. Therefore, North Indian patients may also have a distinct, novel clustering pattern due to unique genetic, epigenetic, and environmental factors. We aim to identify clusters of type 2 diabetes in North Indians and to describe the different characteristics of these clusters. METHODS: The K value for the optimal number of clusters was obtained from two-step clustering. K means clustering was done with this K value using SPSS 29.0 software. Variables used for clustering were age, BMI, HbA1c, HOMA-beta, HOMA-IR, and waist circumference. RESULTS: Four phenotypically different clusters were identified in 469 individuals with type 2 diabetes. Cluster 1 was severe insulin deficient diabetes (15%), Cluster 2 was severe insulin resistant diabetes (22%), Cluster 3 was moderate obesity-related diabetes (35%), and Cluster 4 was moderate age-related diabetes (27%). Clusters 1 and 2 were similar to earlier studies but in different proportions. Clusters 3 and 4 characteristics were different from earlier studies, with greater impairment in beta cell function and higher HbA1c levels. Significant insulin resistance was noted in all clusters. CONCLUSION: The phenotypic clusters of type 2 diabetes identified in the present study were characterized by high levels of insulin deficiency along with important contributions from insulin resistance.

Dyslipidemia in diabetes.

Diabetes mellitus is a metabolic disorder that often predisposes to cardiovascular diseases (CVD). CVD is an important cause of morbidity and mortality in diabetes. The typical diabetic dyslipidaemia is characterized by low HDL cholesterol, high triglycerides with mildly increased or even normal LDL. This attenuated rise in LDL is due to the more atherogenic small dense LDL particles. Genetic factors, obesity, lack of physical activity, alcohol abuse, poorly controlled glucose levels are some of the common risk factors for dyslipidaemia. Non-pharmacological management of dyslipidaemia is important and includes modification in the diet, increase in physical activity and efforts to reduce weight. Statins remain the mainstay of pharmacotherapy for dyslipidaemia in diabetes. Due to the small dense LDL, even patients with diabetes who have normal LDL cholesterol, achieve reduction in cardiovascular risk with statin therapy. Those patients who do not achieve acceptable LDL reductions with statin alone can be treated with combination therapy of ezetimibe with statins. Many novel therapies have also emerged such as bempedoic acid and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors. The targets for LDL cholesterol depend upon the patients underlying cardiovascular risk category. The use of pharmacotherapy for lowering triglycerides in patients with mild to moderate hypertriglyceridemia and diabetes is still a matter of debate. Proper management of dyslipidaemia is critical component of treatment of diabetes mellitus.

High level of psychological stress in COVID-19 recovered individuals: role of copeptin as a potential biomarker.

Background: Study aimed to assess stress in COVID-19 recovered individuals using a validated questionnaire PSS-10 score and stress biomarkers - salivary cortisol and serum copeptin. Methods: A total of 83 subjects of which 54 subjects (66.3%) who were hospitalized were recruited 8-20 weeks following recovery from COVID-19. Stress was assessed by PSS-10 stress-scale after a mean duration of 14.5 weeks after recovery. Sixty-eight subjects (81.9%) had new or persistent symptoms after recovery. Subjects were divided into two groups on the basis of PSS score; mild stress (PSS:0-13) and moderate to severe stress (PSS:>14) and levels of biomarkers (serum copeptin, DHEAS and salivary cortisol) were compared in the two groups. Results: Forty-four subjects (53%) had moderate to severe stress and 39 subjects (47%) had mild stress. Subjects with post COVID symptoms had significantly higher stress levels as compared to subjects who were asymptomatic [15 vs. 9; p = 0.003]. Serum copeptin levels were significantly higher among subjects with moderate to severe stress as compared to those with mild stress [0.41 vs. 0.67 ng/mL; p = 0.031]. Subjects with moderate to severe stress had higher median salivary cortisol compared to subjects with mild stress [1.03 vs. 1.44 nmol/L; p = 0.448]. Conclusion: Our study demonstrated moderate to severe stress in over half and some level of stress in nearly all COVID recovered individuals even after 3 months. Serum copeptin was found to be a useful biomarker to objectively measure stress in these subjects.

Verapamil improves One-Year C-Peptide Levels in Recent Onset Type-1 Diabetes: A Meta-Analysis.

Meta-analysis studying the role of verapamil in improving C-peptide in people with recent-onset type-1 diabetes (T1DM) has not been conducted to date. We undertook this meta-analysis to address this knowledge gap. Electronic databases were systematically reviewed for RCTs having individuals with T1DM receiving verapamil in the treatment arm and placebo in the control arm over the standard of care. The primary outcome was to evaluate changes in the C-peptide area under the curve (AUC) at a one-year follow-up. Secondary outcomes were to assess alterations in C-peptide AUC, glycated hemoglobin (HbA1c), blood pressure, heart rate, and side effects at different time intervals over a one-year follow-up. From the initially screened 27 articles, data from two RCTs (112 patients) satisfied the inclusion criteria and were analyzed. Compared to placebo, C-peptide AUC in individuals receiving verapamil was not different at three months [MD 0.17 nmol/L (95%CI: -0.05-0.38); P = 0.13; I2 = 86%] but significantly higher at 1-year [MD 0.27 nmol/L (95%CI: 0.19-0.35); P < 0.01; I2 = 12%]. The verapamil arm showed similar changes in HbA1C at three months [MD 0.23% (95%CI: -0.43-0.90); P = 0.49; I2 = 88%] and 1-year [MD 0.18% (95% CI: -0.74 - 1.10); P = 0.70; I2 = 89%] compared to placebo. Occurrence of treatment-emergent adverse events [Risk ratio (RR) 1.90 (95%CI: 0.52-6.91); P = 0.33; I2 = 63%], serious adverse events [RR 1.40 (95%CI: 0.50-3.93); P = 0.53], constipation [RR4.11 (95%CI: 0.93-18.13); P = 0.06; I2 = 0%], headache [RR0.48 (95%CI: 0.16-1.43); P = 0.19; I2 = 0%], severe hypoglycemia [RR 0.87 (95%CI: 0.06 - 13.51); P = 0.92] were comparable across groups. Verapamil was well tolerated, and its use over one year was associated with significant improvements in C-peptide AUC though the HbA1c remained unchanged.

Can Bone-Specific Alkaline Phosphatase be a Marker of Vascular Calcification in Type 2 Diabetes Mellitus?

Background and Aims: Alkaline phosphatase (ALP) enzyme has been linked to vascular calcification. Unexplained elevations in serum ALP levels have been reported in patients with type 2 diabetes mellitus (T2DM). We assessed bone-specific alkaline phosphatase (BAP) levels in patients with T2DM who had unexplained ALP elevations and studied the association between BAP and other markers of vascular calcification. Methods: Patients with T2DM who had high serum ALP in the absence of known causes of ALP elevation were studied. The control group was T2DM patients with normal ALP. We measured the serum levels of BAP along with the leptin, fetuin-A, and vitamin K2 levels. Ankle-brachial index (ABI) was also measured in both groups. Results: Serum BAP levels were significantly higher in the group with high ALP when compared with the normal ALP group. A significant positive correlation was present between BAP and serum fetuin-A as well as between BAP and Vit K2 levels. There was no correlation between BAP and serum leptin. ABI was comparable between the two groups. Conclusions: Patients with T2DM may have unexplained elevation in ALP due to an increase in BAP. Elevation in BAP may be associated with other markers of vascular calcification suggesting an increased risk of vascular calcification.

Diabetes reversal: Update on current knowledge and proposal of prediction score parameters for diabetes remission.

BACKGROUND AND AIM: The field of diabetes reversal is continuously evolving. Strategies for implementing diabetes care towards diabetes reversal are still being worked out. We aim to analyse data from available literature to ascertain factors allowing patient centric dietary approach to achieve diabetes reversal in clinical practice. METHODS: In this exploratory review, an update on current knowledge is presented to delineate factors driving diabetes remission in an individual based on major studies in the field. This knowledge is then applied to subtypes of type 2 diabetes to optimise dietary approach for reversal of diabetes. RESULTS AND CONCLUSION: Shorter duration of diabetes, lesser number of medicines needed to achieve euglycemia and 15 kg weight loss are common factors favouring diabetes remission in all major studies. A patient centric approach to diabetes reversal taking into account the recently described diabetes subtypes is being proposed to improve the proportion of patients achieving remission. We also propose the parameters of a novel diabetes remission prediction score, based on patient motivation, interaction with the care-team, level of diabetes self-care and the intent of the care-team.

Prevalence of diabetes related vascular complications in subjects with normal glucose tolerance, prediabetes, newly detected diabetes and known diabetes.

AIMS: Varying prevalence of individual diabetes related vascular complications in prediabetes has been reported. However, very few studies have looked at both macrovascular and microvascular complications in prediabetes. METHODS: Study subjects without any history of diabetes underwent oral glucose tolerance test (OGTT) and were classified as either normal glucose tolerance (NGT), prediabetes (PD), newly detected diabetes mellitus (NDDM) on the basis of American Diabetes Association (ADA) criteria. Age and sex matched known diabetes mellitus (KDM) patients were also recruited. All the participants were subsequently screened for both macrovascular (CAD, CVA,PVD) and microvascular (retinopathy, nephropathy and neuropathy)complications of diabetes. RESULTS: Prevalence of vascular complications among prediabetes subjects was 11.1% as compared to 1.4% among NGT subjects, 13.9% among NDDM subjects and 23.8% among KDM subjects. There was no significant between complication rates in prediabetes and NDDM group (p = 0.060). The prevalence of macrovascular and microvascular complications among prediabetes subjects was 4.2% and 6.9% while the same in NDDM was 4.2% and 9.7%. CONCLUSIONS: The proportion of subjects with prediabetes and vascular complications was about half of those with known diabetes and almost similar to those with newly detected diabetes mellitus.

Changing Trend in Vitamin D Status from 2008 to 2016: An Experience from a Tertiary Care Institute in North India.

BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) assays have become readily available in India over the past decade. A large number of cross-sectional studies have been performed on the vitamin D status and the prevalence of vitamin D deficiency (VDD) in India. However, seasonal and long-term trends in serum 25(OH)D levels have been reported less frequently. AIM: To determine the seasonal and year-wise variation in vitamin D status at a tertiary care hospital in north India. MATERIALS AND METHODS: Using hospital records, the data on serum 25(OH) D assays performed in its endocrinology laboratory between 2008 and 2016 were obtained. For analysis of seasonal trends, the months of a year were divided into following seasons: March to June (summer season), July to October (rainy season), and November to February (winter season). VDD was defined as serum 25(OH)D concentration <20 ng/mL. RESULTS: A total of 26,339 assays of serum 25(OH)D were analyzed in the study. The year-wise assay numbers increased steadily from 2008 to peak in the year 2012, followed by a decline and a second smaller peak in the year 2016. The mean serum 25(OH)D concentration increased from 19.1 ± 16.4 ng/mL in 2008 to 21.7 ± 17.1 ng/mL in 2016 (P = 0.02). Between 2008 and 2016, the prevalence of VDD decreased from 71.9% to 54.3% in females, and from 56.7% to 52.1% in males. The levels in rainy season were significantly higher as compared to winters and summers (P < 0.05 for both). Hypervitaminosis D (serum 25(OH)D >100 ng/mL) and vitamin D toxicity (serum 25(OH)D >150 ng/mL) were seen in 319 (1.2%) and 27 (0.1%) assays, respectively. CONCLUSIONS: This study provides data on seasonal and year-wise trends in vitamin D status over a long period of time at a tertiary care hospital in north India. A long-term trend toward improving vitamin D status, especially in females, was noted in the study. The prevalence of VDD was found to decrease in the analyzed samples during the study period.

Goiter Prevalence and Thyroid Autoimmunity in School Children of Delhi.

INTRODUCTION: Several studies from India, performed prior to 2010, have reported a goiter prevalence of greater than five per cent in school going children. There has been considerable success in universal salt iodization efforts in the past decade. We studied the prevalence of goiter and thyroid autoimmunity in school going children in Delhi between 2010 and 2014 to assess the impact of salt iodization. MATERIALS AND METHODS: The study employed the population proportionate to size (PPS) cluster sampling methodology to select subjects between the age of six and 14 years, from all 34 wards of 9 districts of Delhi. Cluster randomization sampling design was followed and in this way we identified 30 wards, from each of which 90 children were recruited for the study. The total sample size was 2700 children. Estimation of fT3, fT4, TSH, anti-TPO antibodies and urine iodine concentration (UIC) was done for 10% of the study population. RESULTS: The prevalence of goiter in this study in the 6-14 years age group was 6.4%. The prevalence of goiter was higher in females (7.7% compared to 5.3% in males, P = 0.01). In the 270 subjects who were selected for biochemical evaluation, subclinical hypothyroidism was seen in 18.4% and positive anti-TPO antibodies were seen in 14.8%. The median UIC was 150 µg/L. CONCLUSIONS: There is improvement in goiter prevalence in the post-iodization period in Delhi. But still, residual goiter rates are above five per cent suggesting presence of other causes of goiter in this area. There is a high prevalence of thyroid autoimmunity in this population.