Erroneous reduction of HbA1c levels in patients with type 2 diabetes mellitus on dapsone treatment for Hansen's disease - a single-center retrospective cohort study.

Background Dapsone treatment may reduce HbA1c levels in patients with diabetes. Aims To assess the prevalence and characteristics of dapsone associated reduction of HbA1c in patients with Hansen's disease. Methods A retrospective data review of outpatient and inpatient charts of consecutive patients with Hansen's disease and type 2 diabetes mellitus was conducted over two years from January 2014 to January 2016 at the Department of Dermatology, CMC Vellore, India. Results Of the 245 patients with a confirmed diagnosis of Hansen's disease who were on oral dapsone 100 mg/day as part of their treatment regimen, 49 patients had diabetes and were eligible for the study as per predetermined inclusion criteria. Of these, 35 subjects (71%) had an HbA1c discordantly lower than the corresponding mean plasma glucose levels. Patients with discordant HbA1c levels were more likely to be male and to have a higher RBC mean corpuscular volume (MCV). A greater reduction in HbA1c levels was seen during the initial 3 months of therapy of dapsone treatment. Limitations The small sample size and retrospective design were limitations of this study. Also, we did not analyze the role of methemoglobinemia or the utility of alternative measures of glycemic control in these patients. Conclusion We describe a high prevalence of dapsone associated inappropriate HbA1c lowering in type 2 diabetes mellitus patients. This may have serious implications for the management of diabetes in patients on therapy with dapsone.

Characterizing progressive beta-cell recovery after new-onset DKA in COVID-19 provoked A-ß+ KPD (ketosis-prone diabetes): A prospective study from Eastern India.

BACKGROUND: Recent literature suggests a bi-directional relationship between COVID-19 infection and diabetes mellitus, with an increasing number of previously normoglycemic adults with COVID-19 being admitted with new-onset diabetic ketoacidosis (DKA). However, the possibility of COVID-19 being a potential trigger for A-ß + ketosis-prone diabetes (KPD) in these patients needs elucidation. Our study aimed at analyzing such a cohort of patients and determining their natural course of ß-cell recovery on serial follow-up. METHODS: After initial screening, n = 42 previously non-diabetic patients with new-onset DKA and RT-PCR positive COVID-19, were included in our ten-month follow-up study. Of these, n = 22 were negative (suspected A-ß + KPD) and n = 20 were positive (Type 1A DM) for autoantibodies (GAD/IA-2/ZnT8). Subsequently, n = 19 suspected KPD and n = 18 Type 1A DM patients were followed-up over ten months with serial assessments of clinical, biochemical and ß-cell secretion. Amongst the former, n = 15 (79%) patients achieved insulin independence, while n = 4 (21%) continued to require insulin at ten-months follow-up. RESULTS: On comparison, the suspected KPD patients showed significantly greater BMI, age, Hba1c, IL-6 and worse DKA parameters at presentation. Serial C-peptide estimations demonstrated significant ß-cell recovery in KPD group, with complete recovery seen in the 15 patients who became insulin independent on follow-up. Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were associated with poorer recovery of ß-cell secretion at ten-month follow-up amongst the KPD patients, CONCLUSIONS: This is the first prospective study to demonstrate progressive recovery of ß-cell secretion in new-onset A-ß + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM. Given their significant potential for ß-cell recovery, meticulous follow-up involving C-peptide estimations can help guide treatment and avoid injudicious use of insulin.

Exogenous recombinant human insulin-induced severe hypersensitivity reaction precipitating hyperglycemic crisis: A clinical conundrum.

Hypersensitivity reactions against exogenous insulin are a rare clinical entity after the advent of recombinant human insulin; however, there are still case reports wherein patients develop hypersensitivity reactions against insulin. We present the case of a type 1 diabetes mellitus patient who developed type 1 hypersensitivity reaction against subcutaneous insulin. He had recurrent episodes of diabetic ketoacidosis after developing hypersensitivity reactions against insulin, requiring multiple hospital admissions. When he presented to us, he was on both insulin infusion and subcutaneous insulin, requiring a daily insulin dose of about 800 units and having severe insulin hypersensitivity reactions and hyperglycemia. He had multiple subcutaneous erythematous nodules at the insulin injection sites, however, had no evidence of systemic allergy. Investigations revealed eosinophilic leukocytosis, and high IgE levels and skin biopsy showing evidence of insulin hypersensitivity. He was desensitized to insulin according to Heinzerling et al. insulin desensitization protocol and subsequently with immunomodulation therapy using steroids (pulse methylprednisolone) and mycophenolate mofetil as well as by installation of insulin pump.

An uncommon cause of polyarthralgia.

Tumour induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting and hypophosphatemic osteomalacia, caused by FGF-23 (Fibroblast growth factor-23) producing mesenchymal tumours. Here, we report the case of a 40 year old lady referred by her family physician for multiple joint pains of 2 years duration. There was no evidence of inflammatory arthritis. Biochemical investigations revealed low phosphorus, with raised alkaline phosphatase and high levels of FGF-23. As a TIO was considered likely, functional imaging with a DOTATATE PET scan was done, which revealed a DOTA avid lesion in the right foot. Following surgical excision of the tumour, there was significant relief in symptoms and gradual recovery of phosphate to normal levels. It is relevant and important for family physicians as in subjects with symptom like polyarthralgia, a simple measurement of analytes like phosphate, calcium and alkaline phosphatase in primary care setting will help to arrive at a cause and referral for further evaluation as this condition is potentially treatable.

Clinico-radiological characteristics and not laboratory markers are useful in diagnosing diabetic myonecrosis in Asian Indian patients with type 2 diabetes mellitus: A 10-year experience from South India.

INTRODUCTION: Diabetic myonecrosis or muscle infarction is an unusual complication of Type 2 Diabetes, usually associated with longstanding disease. It commonly presents as an acute non-traumatic palpable swelling of the affected muscle with predilection for the quadriceps and thigh muscles, often accompanied by retinopathy and nephropathy. METHODOLOGY: A retrospective review of the medical records of patients admitted with diabetic myonecrosis under the Department of Endocrinology, Christian Medical College Vellore over a period of ten years(2006-2015) was done. Data pertaining to clinical, biochemical and radiological characteristics were obtained and treatment modalities and outcomes were recorded. RESULTS AND ANALYSIS: A total of n = 4 patients with diabetic myonecrosis and completed clinical data were included in the study. In our present series, the mean age at presentation was 45.5 years (±7.3 years), the mean duration of the diabetes was 9.0 years (±2.5 years)with an equal distribution of male and female subjects. The mean HbA1c (9.5 ± 0.6%) was suggestive of poor glycemic control at presentation with all (100%) the patients in our series having concomitant one or more microvascular complications. While laboratory parameters of elevated CPK or LDH were mostly normal, the findings of T1 hyperintense and T2 hypointense heterogenous lower limb lesions were present in all the subjects (n = 4). Conservative management with bed rest, analgesics and good glycemic control were effective in good clinical improvement over a period of 1-2 months. CONCLUSIONS: Our series of diabetic myonecrosis in Indian patients with Type 2 diabetes mellitus, elucidates the varied clinical presentations, with MRI findings rather than laboratory markers being the mainstay of diagnosis.

Are Predictive Equations for Estimating Resting Energy Expenditure Accurate in Asian Indian Male Weightlifters?

BACKGROUND: The accuracy of existing predictive equations to determine the resting energy expenditure (REE) of professional weightlifters remains scarcely studied. Our study aimed at assessing the REE of male Asian Indian weightlifters with indirect calorimetry and to compare the measured REE (mREE) with published equations. A new equation using potential anthropometric variables to predict REE was also evaluated. MATERIALS AND METHODS: REE was measured on 30 male professional weightlifters aged between 17 and 28 years using indirect calorimetry and compared with the eight formulas predicted by Harris-Benedicts, Mifflin-St. Jeor, FAO/WHO/UNU, ICMR, Cunninghams, Owen, Katch-McArdle, and Nelson. Pearson correlation coefficient, intraclass correlation coefficient, and multiple linear regression analysis were carried out to study the agreement between the different methods, association with anthropometric variables, and to formulate a new prediction equation for this population. RESULTS: Pearson correlation coefficients between mREE and the anthropometric variables showed positive significance with suprailiac skinfold thickness, lean body mass (LBM), waist circumference, hip circumference, bone mineral mass, and body mass. All eight predictive equations underestimated the REE of the weightlifters when compared with the mREE. The highest mean difference was 636 kcal/day (Owen, 1986) and the lowest difference was 375 kcal/day (Cunninghams, 1980). Multiple linear regression done stepwise showed that LBM was the only significant determinant of REE in this group of sportspersons. A new equation using LBM as the independent variable for calculating REE was computed. REE for weightlifters = -164.065 + 0.039 (LBM) (confidence interval -1122.984, 794.854]. This new equation reduced the mean difference with mREE by 2.36 + 369.15 kcal/day (standard error = 67.40). CONCLUSION: The significant finding of this study was that all the prediction equations underestimated the REE. The LBM was the sole determinant of REE in this population. In the absence of indirect calorimetry, the REE equation developed by us using LBM is a better predictor for calculating REE of professional male weightlifters of this region.

Indirect Calorimetry: From Bench to Bedside.

Accurate determination of energy expenditure (EE) is vitally important yet often neglected in clinical practice. Indirect calorimetry (IC) provides one of the most sensitive, accurate, and noninvasive measurements of EE in an individual. Over the last couple of decades, this technique has been applied to clinical circumstances such as acute illness and parenteral nutrition. Beyond assessing the nutritional needs, it has also shed light on various aspects of nutrient assimilation, thermogenesis, the energetics of physical exercise, and the pathogenesis of obesity and diabetes. However, because of little or no experience with IC provided during medical education, the benefits of IC are poorly appreciated. Newer technology, cost-effectiveness, and a better understanding of how to interpret measurements should lead to more frequent use of IC. This review focuses on the physicochemical background of IC, the various indications for use, techniques and instruments, potential pitfalls in measurement, and the recent advances in technology that has adapted the technique to long-term studies in humans.

Clinical characteristics, beta-cell dysfunction and treatment outcomes in patients with A-ß+ Ketosis-Prone Diabetes (KPD): The first identified cohort amongst Asian Indians.

OBJECTIVE: Ketosis-prone diabetes (KPD), an atypical form of diabetes, has emerged as a heterogeneous syndrome in multiple ethnic groups. The objectives of this study were to look into the clinical characteristics of adult Asian Indian patients with recently diagnosed, antibody negative diabetes presenting with unprovoked ketoacidosis (A-ß+ KPD) and to determine the natural course of recovery of beta-cell functions on serial follow-up over one year. RESEARCH DESIGN AND METHODS: Newly diagnosed adult diabetes patients (n=11) with suspected KPD (A-ß+) were prospectively studied over a period of 1-year with serial evaluations of clinical, biochemical and beta-cell secretion characteristics. These were compared with a control group (n=23) of KPD (A+ß-) (classical Type 1A diabetes) with similar presentation. Beta-cell secretion was assessed by fasting and stimulated C-peptide values after a standard mixed meal challenge. Glycaemic control and treatment outcomes were also documented. RESULTS: In comparison to the A+ß- KPD controls, the A-ß+ KPD patients had a significantly older age, higher BMI, stronger family history of type 2 diabetes, more severe ketoacidosis and higher fasting and stimulated C-peptide level at presentation. On serial follow-up, the patients with KPD achieved complete recovery of their beta-cell function with remission from insulin-dependence within 3-4months without further recurrences of DKA. CONCLUSIONS: This is the first reported series of A-ß+ KPD from India. The phenotype of Indian A-ß+ KPD patients differs from their Western counterparts in that they are relatively younger and leaner, though the male preponderance and natural history of recovery of beta-cell dysfunction bears similarity.