Once-weekly Insulin Icodec as Compared to Once-daily Basal Insulins: A Meta-analysis.

BACKGROUND: Once-weekly basal insulin icodec has been tested in clinical trials for efficacy and safety over currently available glargine-100 and degludec in different clinical settings for type 2 diabetes. We performed this meta-analysis to evaluate its overall safety and efficacy as compared to glargine-100 and degludec (nonicodec), from all available randomized controlled trials. METHODS: Seven trials comparing once-daily basal insulin analogs to once-weekly basal insulin icodec were included. Based on available information, outcomes in terms of HbA1c, fasting plasma glucose reduction, and increase in time in range (TIR) were compared. Side-effects were compared for overall hypoglycemia, severe hypoglycemia, and weight gain. The pooled effect size for continuously distributed data was measured as a reduction in "estimated differences in mean (with 95% CI)." For categorical data, the pooled effect size was measured as the Mantel-Haenszel risk ratio (with 95% CI). RESULTS: Analyzing against the nonicodec comparators together, the "estimated mean changes" in HbA1c and fasting plasma glucose favoring icodec were -0.22% (-0.35, -0.10) and -1.59 mg% (-9.26, 6.08) respectively. The "estimated mean increment" in weight for icodec was 0.64 kg (0.61, 0.67). The "estimated mean percentage" increment in TIR for icodec was 4.24% (2.99, 5.49). The Mantel-Haenszel risk ratios for all hypoglycemic events and severe hypoglycemia for icodec were 1.24 (1.02, 1.50) (P = .03) and 0.81 (0.31, 2.08) (P is not significant), respectively, suggesting a 24% increased incidence of all hypoglycemia with icodec. CONCLUSION: Once-weekly basal insulin icodec as compared to once-daily basal insulin analogs had a slight increase in the risk of overall hypoglycemia and weight gain, without any difference in severe hypoglycemia, with similar glycemic control (in terms of fasting plasma glucose, HbA1c, and TIR).

Different Sodium-Glucose Cotransporter-2 Inhibitors: Can They Prevent Death?

OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) in cardiovascular outcome trials (CVOTs) demonstrate cardiovascular (CV) safety and benefits. Some dedicated randomized controlled trials (RCTs) demonstrate benefit in terms of renal outcomes and hospitalization due to heart failure (HF). RCTs report differences in the secondary outcomes with respect to mortality (CV and/or all-cause). We undertook a meta-analysis of all SGLT2is for which in addition to CVOT, HF outcome/renal outcome studies are available to establish whether individual SGLT2is were able to prevent death. METHODS: We included available event-driven randomized, placebo-controlled CVOTs and dedicated RCTs of SGLT2is exploring renal outcomes and HF. We included 3 trials of empagliflozin, 3 of dapagliflozin, 2 of canagliflozin, and 2 of sotagliflozin. The efficacy outcomes included all-cause mortality and CV mortality. Hazard ratios (HRs) with 95% CIs were pooled for individual molecules. RESULTS: The HR for all-cause mortality including all trials was 0.86 (0.80-0.93). The HRs for all-cause mortality in empagliflozin (N = 16 738), dapagliflozin (N = 26 208), canagliflozin (N = 14 543), and sotagliflozin (N = 11 806) were 0.86 (0.69-1.08), 0.83 (0.72-0.97), 0.86 (0.75-0.97), and 0.95 (0.81-1.11), respectively. The HR for CV mortality including all trials was 0.85 (0.78-0.92). The HRs for CV mortality in empagliflozin, dapagliflozin, sotagliflozin, and canagliflozin were 0.81 (0.63-1.03), 0.88 (0.78-1.00), 0.89 (0.74-1.07), and 0.84 (0.72-0.98), respectively. CONCLUSION: SGLT2is as a class reduce both all-cause mortality and CV mortality. Canagliflozin possibly reduces both all-cause mortality and CV mortality, whereas dapagliflozin may reduce all-cause mortality but not CV mortality. Empagliflozin and sotagliflozin may reduce neither.

Management of Hypertension in Patients with Diabetes: A Comprehensive Review of the Perceptions and Practices of Health Care Providers in India.

OBJECTIVES: This study evaluated the perception and practices of health care providers (physicians, diabetologists, and endocrinologists) regarding the treatment of hypertension in patients with diabetes in India. METHODS: Health care providers throughout India who treated patients with diabetes and hypertension were invited to participate in an online survey and periodic 21 virtual meetings. They were questioned about their perception and practices in managing these patients, and strategies to improve blood pressure (BP). RESULTS: The online survey was completed by 2,513 health care providers, and 344 participated in virtual meetings. More than 50% reported that 31-50% of their patients with diabetes also had hypertension. Home BP monitoring was recommended by 88%, and lifestyle modifications were consistently recommended. Choice of antihypertensive treatment varied based on comorbidities, and a renin-angiotensin system blocker plus a calcium channel blocker (CCB) was the most common combination for dual antihypertensive therapy. Suggested strategies to improve BP control included patient awareness/education, lifestyle modifications, better follow-up/monitoring, and optimization of therapy. CONCLUSION: Indian health care providers were aware of clinical recommendations and practices regarding treatment of patients with diabetes and hypertension, and generally make clinical decisions consistent with current guidelines. Optimization of care for these patients is essential to reduce cardiovascular disease risk and improve patient outcomes.

Assessment of Insulin Resistance Indices in Individuals with Lean and Obese Metabolic Syndrome Compared to Normal Individuals: A Population Based Study.

INTRODUCTION: Obesity is associated with insulin resistance and measuring it in an apparently healthy population and correlating them with established risk parameters may identify predisposed individuals who may later develop diabetes or cardiovascular diseases. MATERIAL AND METHODS: 405 participants from a rural area were investigated for various metabolic parameters and indices of insulin resistance. Insulin resistance indices were evaluated in the 3 different groups [Obese Metabolic Syndrome (MetS), Lean MetS and those without MetS]. Various anthropometric and metabolic parameters were compared. Lean MetS is defined as those having waist criteria below the region specific waist criteria and even then satisfying the definition of MetS as per the NCEP ATP-III criteria. RESULTS: The mean fasting insulin level was 7.69+4.38 uIU/ml in normal population, 10.40+5.65 uIU/ml in Lean MetS population and 13.71+6.63 uIU/ml in Obese MetS population (P<0.05). The HOMA-IR2 measured was 2.39+ 1.69 in normal population, while in the Lean MetS and Obese Mets were 3.99+3.40 and 4.04+2.53, respectively (P<0.05). The QUICKI level measured was 0.358+0.041 in normal population and 0.334+0.037 and 0.316+0.026 respectively in the Lean MetS and Obese MetS (P<0.05). McAuley index measured in normal population was 0.49+0.26 and 0.75+0.25 and 0.79+0.17 in the Lean MetS and Obese MetS population (P<0.05).TyG index measured was 8.51+0.46 in normal population and 9.27+0.56 and 9.06+0.49 respectively in the Lean MetS and Obese MetS (P<0.05). CONCLUSION: Insulin resistance indices are elevated in MetS compared to the normal population but the indices in Lean MetS are not different from Obese MetS. The relevance of ethnicity specific waist circumference may need re-evaluation considering its little impact in influencing the level of insulin resistance.

Insulin Access Enhancement in India: Expert Views on Integrating Interchangeable Biosimilar Insulin Glargine.

Achieving and maintaining optimal glycemic targets is the fundamental goal of the management of diabetes. However, failure of oral antidiabetic drugs (OADs) to sustain the targeted glycemic levels in individuals with progressing disease often requires initiation of insulin therapy. This article consolidates the expert opinions of 377 doctors who participated in 34 advisory board meetings held digitally (n=23) and in person (n=11) across India. The present report underscores the need for readily available alternatives, such as biosimilar insulins, in the Indian healthcare market to make insulin accessible to every patient with diabetes. The introduction of biosimilar insulins in the Indian healthcare market is the key to making insulin accessible to every patient with diabetes. Biosimilars are biologic products that closely resemble reference/originator biologics and demonstrate no clinically meaningful differences in safety and effectiveness. The concept of interchangeability serves as a pivotal differentiator for biosimilars, underlining their reliability and safety, and plays a significant role in their broader acceptance and integration into healthcare systems. The 'interchangeability' designation by the United States Food and Drug Administration (USFDA) elevates the biosimilar concept, promoting faster and broader adoption of insulin biosimilars, especially benefiting patients prone to non-adherence to insulin therapy. Healthcare providers are encouraged to consider the option of initiating or transitioning to biosimilar insulin glargine to address the insulin accessibility challenges.

Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Sustained-Release Vildagliptin 100 mg in Type 2 Diabetes Mellitus: A Review.

Dipeptidyl peptidase-4 inhibitors (DPP4Is) were introduced into the management of type 2 diabetes mellitus (T2DM) as they are insulinotropic and have no inherent risk of hypoglycemia and no effect on body weight. Currently, 11 drugs in this class are available for the management of diabetes. Although they have a similar mechanism of action, they differ from one other in their binding mechanisms, which influences their therapeutic and pharmacological profiles. Vildagliptin's overall safety and tolerability profile was comparable to placebo throughout clinical studies, and real-world data in a large group of T2DM patients corroborated this finding. Therefore, DPP4Is like vildagliptin is a secure alternative for treating patients with T2DM. Vildagliptin treatment given as a once-daily (QD) 100 mg sustained release (SR) formulation fits the criteria of adherence and compliance. This SR formulation, given once daily has the potential to provide glycemic control like the vildagliptin 50 mg twice-daily (BD) formulation. This comprehensive review discusses the journey of vildagliptin as 50 mg BD therapy as well as 100 mg SR QD therapy.

SGLT2 Inhibitors: Effect on Myocardial Infarction and Stroke in Type 2 Diabetes.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently been recommended as preferred agents for management of hyperglycemia in type 2 diabetes, primarily based on their ability to reduce a composite of major cardiovascular adverse events (3-point major adverse cardiovascular events [MACE]), predominantly by reducing cardiovascular death. However, reduction of the individual components, myocardial infarction (MI), or stroke (fatal and nonfatal) events have not been well explored. METHODS: In this meta-analysis, we included data available from cardiovascular outcome trials only, which were event-driven, randomized, and placebo-controlled. Pooled efficacy outcomes included Mantel Haenszel (MH) risk ratio using fixed model (with 95% CI) for fatal and nonfatal MI, stroke, and total MI and stroke. FINDINGS: Data from 4 eligible trials included 42,568 subjects. Total MACE, MI, and stroke were reported in 4176, 2157, and 1288 subjects, respectively. SGLT2is did not significantly reduce either MI or stroke individually or in totality. The MH risk ratio (95% CI) for fatal and nonfatal MI and stroke with different SGLT2is was found to be 0.93 (95% CI, 0.85-1.01) and 1.00 (95% CI, 0.89-1.11), respectively. For total atherosclerotic cardiovascular disease (ASCVD) events, MH risk ratio (95% CI) was 0.95 (95% CI, 0.89-1.02). For all nonfatal ASCVD (combined nonfatal MI and nonfatal stroke), MH risk ratio (95% CI) was 0.94 (95% CI, 0.88-1.02). INTERPRETATION: SGLT2is reduce MACE without any discernable significant reduction of the incidence of MI or stroke (fatal and nonfatal), probably implicating mechanisms unrelated to anti-atherogenic effects.

Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Real world study of short term efficacy, safety, and tolerability of canagliflozin 100 mg initiation in type 2 diabetes mellitus patients during hot humid Indian summer.

BACKGROUND AND AIM: To assess short term (3 months) efficacy, safety, and tolerability of canagliflozin 100 mg among type 2 diabetes mellitus (T2DM) initiated during hot humid Indian summer. METHODS: A prospective, observational, multi-center study of 300 T2DM patients with inadequate glycemic control (i.e., HbA1c of ≥6.5%) with or without other antihyperglycemic agents (AHA) were enrolled in the study in the month of March. The objective of the study was to assess the efficacy that is changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), blood pressure (BP), lipid profile, body mass index (BMI) and safety of canagliflozin with regards to genitourinary infection, fall, diabetic keto acidosis (DKA) episodes, blood ketone and beta-hydroxybutyrate levels. All patients were initiated on canagliflozin 100 mg once daily for 12 weeks, irrespective of background medications. RESULTS: At 12 weeks, a significant reduction was observed in all the glycemic parameters,BMI, BP, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, a nonsignificant reduction in estimated glomerular filtration rate (eGFR) was observed at 12 weeks. A total of 9 adverse events were reported including 2 episodes of urinary tract infection (UTI) and 4 episodes of genital infection. The blood ketone, beta-hydroxybutyrate levels were found to be within normal limits and no episode of DKA was reported at 12 weeks. None of our patients had reported any volume depletion related adverse events viz. postural hypotension, giddiness etc. CONCLUSION: Canagliflozin 100 mg can be safely initiated in type 2 diabetes patients during hot humid Indian summer, irrespective of background medications and is effective and well tolerated.

Lipid Profile in Infant.

INTRODUCTION: Alteration in lipid parameters at birth has a strong association with the development of cardiovascular disease in later life. MATERIAL AND METHODS: Sixty-one infants below the age of 6 months underwent evaluation of lipid parameters. The infants studied were categorized into two groups of ≤4 and >4 weeks of age, wherein their lipid parameters were compared. RESULTS: The normal distribution of lipid parameters of infants <6 months was generated. The mean total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol was 126.2 ± 26.5, 149.1 ± 48.6, 40.7 ± 14.6, and 69.4 ± 19.4 mg/dl, respectively. The total cholesterol and LDL-cholesterol measured in ≤4 and >4 weeks of age groups were statistically not different (total cholesterol 125.0 ± 30.1 mg/dl vs 127.4 ± 23.4 mg/dl, P = 0.727, and LDL-cholesterol 66.0 ± 19.2 mg/dl vs 75.4 ± 21.2 mg/dl, P = 0.780). However, the HDL-cholesterol and triglycerides measured at ≤4 weeks versus >4 weeks age groups were statistically different (HDL-cholesterol 44.9 ± 17.2 mg/dl vs 36.9 ± 10.8 mg/dl, P = 0.031, and triglyceride 147.4 ± 60.2 mg/dl vs 186.5 ± 75.7 mg/dl, P = 0.030). CONCLUSION: The mean lipid parameters were significantly more atherogenic compared to the Western population. Triglyceride levels and HDL-cholesterol levels change significantly after 4 weeks of age compared to that observed before 4 weeks of age.

Effects of DPP4 Inhibitors on Renal Outcomes in Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVES: This meta-analysis of randomized clinical trials (RCT) intends to evaluate the efficacy of DPP4 Inhibitors (DPP4I) compared with placebo, other antidiabetics (or DPP4I) on renal outcomes, adverse events (AEs), and all-cause mortality. METHODS: We searched relevant scientific database for RCTs with DPP4I and prespecified renal end point. The effect size (mean difference or risk ratio) was reported with its 95% confidence interval. RESULTS: Eight RCTs (n = 39040 participants) were included in the analysis. The rate of change in eGFR was not different in DPP4 inhibitor and control group. DPP4I use beyond 52 weeks did not worsen albuminuria progression (RR 0.88; 95% CI 0.80 to 0.96; high quality evidence) compared to placebo. The risk of AEs within 52 weeks (RR 0.93; 95% CI 0.80 to 1.08; moderate quality evidence), beyond 52 weeks (RR 0.98; 95% CI 0.97 to 1.00; low quality evidence), and all-cause mortality (RR 1.04; 95% CI 0.96 to 1.12; very low quality evidence) were similar to placebo. In head-to-head comparison between two DPP4I studies, no significant differences were found between alogliptin and vildagliptin for improvement in eGFR, UACR, or AE at 24 weeks. CONCLUSIONS: DPP4I do not seem to provide persuasive benefit in the renal outcomes or all-cause mortality in diabetes mellitus, though there was no evidence for increased AEs.

Incretins in fibrocalculous pancreatic diabetes: A unique subtype of pancreatogenic diabetes.

BACKGROUND: Studies evaluating endocrine and exocrine functions in fibrocalculous pancreatic diabetes (FCPD) are scarce. METHODS: Insulin, C-peptide, glucagon, incretin hormones (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide [GIP]), and dipeptidyl peptidase IV (DPP-IV) were estimated in patients with FCPD (n = 20), type 2 diabetes mellitus (T2DM) (n = 20), and controls (n = 20) in fasting and 60 minutes after 75 g glucose. RESULTS: Fasting and post-glucose C-peptide and insulin in FCPD were lower than that of T2DM and controls. Plasma glucagon decreased after glucose load in controls (3.72, 2.29), but increased in T2DM (4.01, 5.73), and remained unchanged in FCPD (3.44, 3.44). Active GLP-1 (pmol/L) after glucose load increased in FCPD (6.14 to 9.72, P = <.001), in T2DM (2.87 to 4.62, P < .001), and in controls (3.91 to 6.13, P < .001). Median active GLP-1 in FCPD, both in fasting and post-glucose state (6.14, 9.72), was twice that of T2DM (2.87, 4.62) and 1.5 times that of controls (3.91, 6.13) (P < .001 for all). Post-glucose GIP (pmol/L) increased in all: FCPD (15.83 to 94.14), T2DM (21.85 to 88.29), and control (13.00 to 74.65) (P < .001 for all). GIP was not different between groups. DPP-IV concentration (ng/mL) increased in controls (1578.54, 3012.00) and FCPD (1609.95, 1995.42), but not in T2DM (1204.50, 1939.50) (P = .131). DPP-IV between the three groups was not different. Fecal elastase was low in FCPD compared with T2DM controls. CONCLUSIONS: In FCPD, basal C-peptide and glucagon are low, and glucagon does not increase after glucose load. GLP-1, but not GIP, in FCPD increases 1.5 to 2 times as compared with T2DM and controls (fasting and post glucose) without differences in DPP-IV.

Diagnosis and Management Considerations in Steroid-Related Hyperglycemia in COVID-19: A Position Statement from the Endocrine Society of India.

The current coronavirus disease (COVID-19) pandemic is showing no signs of abatement and result in significant morbidity and mortality in the infected patients. Many therapeutic agents ranging widely between antivirals and anti-inflammatory drugs have been used to mitigate the disease burden. In the deluge of the drugs being used for COVID-19 infection, glucocorticoids (GCs) stand out by reducing mortality amongst in-hospital severe-to-critically ill patients. Health-care practitioners have seen this as a glimmer of hope and started using these drugs more frequently than ever in clinical practice. The fear of mortality in the short term has overridden the concern of adverse long-term consequences with steroid use. The ease of availability, low cost, and apparent clinical improvement in the short term have led to the unscrupulous use of the steroids even in mild COVID-19 patients including self-medication with steroids. The use of GCs has led to the increasing incidence of hyperglycemia and consequent acute complications of diabetic ketoacidosis and mucormycosis in COVID-19 patients. There is an urgent need to dissipate information about optimum management of hyperglycemia during steroid use. In view of this, the Endocrine Society of India has formulated this position statement about the diagnosis and management of hyperglycemia due to the use of GCs in patients with COVID-19 infection.

Cardiovascular safety of Glimepiride: An indirect comparison from CAROLINA and CARMELINA.

BACKGROUND: Despite having unquestionable glucose lowering efficacy, current guidelines no more favour the uses of sulphonylureas for CV safety concern, except when cost is an issue. However, formal cardiovascular outcome trial (CVOT) is not available. MATERIALS AND METHODS: We performed an indirect treatment comparison to find the hazard ratio for 3-point MACE, all-cause death, CV death and non-CV death between glimepiride and placebo based on two large CVOTs which established the CV safety of linagliptin (CARMELINA and CAROLINA). RESULTS: Glimepiride was shown to have a non-inferior risk compared to placebo for 3-point MACE (HR 1.04, 95% CI 0.850, 1.274), all-cause mortality (HR 1.08, 95% CI 0.880, 1.317), CV death (HR 0.96, 95% CI 0.732, 1.259), and non-CV death (HR 1.24, 95% CI 0.893, 1.733). CONCLUSION: Cardiovascular safety of glimepiride is re-assuring and may help patients with type 2 diabetes world-over to avail the benefit of this affordable efficacious medication.

Profile of Auto-antibodies (Disease Related and Other) in Children with Type 1 Diabetes.

BACKGROUND: Type 1 diabetes is associated with several disease-related and other organ-specific autoimmune disorders. Data related to various auto-antibodies in Type 1 diabetes in India is limited. MATERIALS AND METHODS: In this cross sectional study, 92 subjects with T1DM (33 males, 59 females) were evaluated for T1DM related antibodies (autoantibodies to glutamic acid decarboxylase (anti-GAD), autoantibodies to protein tyrosine phosphatise (anti-IA2), anti-islet cell antibody (ICA), insulin autoantibody (IAA), anti-Zinc Transporter(ZnT8) and other organ specific auto antibodies like anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TgAb), IgA anti-tissue transglutaminase (IgA anti-tTG), anti-21-hydroxylase, and anti-ovarian antibody (in females). RESULTS: Anti-GAD, IA-2, islet cell antibody, insulin autoantibodies (IAA), ZnT8 antibody were present in 79.3%, 32.6%, 61.9%, 63%, and 20.65% subjects, respectively. Only 2.2% patients with Type 1 diabetes were antibody negative. At least one antibody was found in 97.8% and at least two antibodies in 67.3%. The presence of anti-TPO, anti-thyroglobulin, IgA anti-tissue transglutaminase, anti 21-hydroxylase were found in 51%, 25%, 22.8%, and 2.1%, respectively. Anti-ovarian antibody was absent in all females of our study population. The duration of diabetes positively correlated with the number of T1DM specific antibody and also with GAD antibody positivity. Anti TPO positivity correlated with the age of onset of T1DM, but not with the duration of disease or presence of other T1DM specific autoantibody. CONCLUSIONS: T1DM is associated with a high prevalence of autoantibodies and antibody negative T1DM is rare. The association with other organ specific antibody (especially thyroid and adrenal glands) and celiac disease is also substantial, which reinforces the importance of regular thyroid and celiac disease screening in T1DM subjects. The duration of diabetes positively correlated with number of T1DM specific antibodies.

Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement.

Diabetic kidney disease (DKD) occurs in approximately 20-40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (- 21.0%, confidence interval [CI] - 34.1 to - 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52-0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48-0.64, p < 0.0001) with SGLT2i, irrespective of baseline estimated glomerular filtration rate. Thus, there is emerging evidence that SGLT2i may be used to curb the mortality and improve the quality of life in patients with DKD. However, clinicians need to effectively select candidates for SGLT2i therapy. In this consensus statement, we have qualitatively synthesized evidence demonstrating the renal effects of SGLT2i and proposed recommendations for optimal use of SGLT2i to effectively manage and delay progression of DKD.

Uric Acid and Its Correlation with Various Metabolic Parameters: A Population-Based Study.

INTRODUCTION: Uric acid, apparently an inert waste product, was found to have association with various metabolic disorders. The data regarding prevalence of serum uric acid (SUA) abnormalities and its correlation with other anthropo-metabolic parameters, however, are scanty. MATERIALS AND METHODS: In all, 405 participants from a rural area were investigated for various metabolic parameters including uric acid. SUA level was evaluated for having any correlation with other anthropometric and metabolic disorders like obesity, dyslipidemia, metabolic syndrome (MetS), hypertension, calcium and vitamin D abnormalities, liver function, and glycemic alterations. Lean MetS is defined as those having waist criteria below the region specific waist criteria and even then satisfying the definition of MetS as per the National Cholesterol Education Program (NCEP) ATP-III (Adult Treatment Panel) criteria. RESULTS: The mean uric acid was 4.2 mg/dL (±1.35), with 4.9 mg/dL (±1.28) for males and 3.7 mg/dL (±1.14) for females. Thirteen of 405 people (3.2%) found to have uric acid level of more than 7.0 mg/dL, and eight people out of 405 (2.0%) had hypouricemia. SUA showed correlation with age, blood pressure, and the anthropometric parameters for obesity, for example, weight, body mass index, waist circumference, waist hip ratio, waist height ratio, fasting insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. However, fasting glucose, calcium, phosphate, 25-hydroxy vitamin D3, and iPTH did not show any correlation with the SUA level. Compared to the healthy population, SUA level was elevated in MetS as defined by International Diabetes Federation (IDF) criteria. However, the SUA in healthy population was not significantly different from the Lean MetS, and SUA of Lean MetS was not significantly different from Obese MetS. CONCLUSION: SUA is elevated in MetS compared to the normal population. However, SUA in Lean MetS is not different from Obese MetS.

Pandemic of Vitamin D Deficiency: Cardiometabolic Concern or Skeletal Biochemical Abnormality?

CONTEXT: Biochemical Vitamin D deficiency is said to be present universally in recent times. However, its effect is more profound in modulation of anthropometric and biochemical risk factors of various chronic metabolic disorders rather than its influence on bone mineral abnormalities. The present study was undertaken to compare various anthropometric and biochemical parameters including basic bone mineral biochemistry in various strata of Vitamin D status. MATERIALS AND METHODS: A population based study was done in the rural area of West Bengal comprising 405 people (initially targeted 400) to look for various anthropometric and biochemical parameters. RESULTS: Anthropometric metabolic markers like BMI, WC, waist to height ratio and biochemical parameters like total cholesterol, LDL, TG, insulin, ALT, FPG were statistically significantly higher in vitamin D deficient (<20 ng/ml) (n = 228) subjects compared to Vitamin D non-deficient subjects (≥20 ng/ml) (n = 177) which persisted even after adjustment for BMI except for FPG. The difference was similarly present when severely Vitamin D deficient (<10 ng/ml) (n = 39) subjects were compared to Vitamin D sufficient subjects (≥30 ng/ml) (n = 38) and persisted after adjustment for BMI except for FPG. However, WHR, blood pressure (both systolic and diastolic), HbA1c, HDL, AST, Uric acid, freeT4, TSH, HOMA-IR were not different in both the above-mentioned comparisons. Metabolic syndrome was statistically significantly lower in vitamin D non-deficient subjects. Though iPTH was statistically significantly higher in the low vitamin D cohorts in both the comparisons, bone mineral markers like serum calcium, phosphorus and alkaline phosphatase were not different even when severely vitamin D deficient subjects were compared to vitamin D sufficient subjects. CONCLUSION: Pandemic of vitamin D deficiency is more likely to be associated with cardio-metabolic risk factors than biochemical bone mineral abnormality.