Clinical Evidence and Practice-Based Guidelines on the Utility of Basal Insulin Combined Oral Therapy (Metformin and Glimepiride) in the Current Era.

BACKGROUND AND AIM: Basal insulin combined oral therapy consisting of insulin and oral anti-diabetic drugs (OADs) is recommended for type 2 diabetes uncontrolled on OADs. There is a lack of clear evidence and recommendations on the combined use of basal insulin analogues to more than one OADs (glimepiride plus metformin) in effective control of glycemic parameters and its safety in terms of reduced hypoglycemic events, weight gain and cardiovascular risk. In this context, a group of clinical experts discussed the utility of basal insulin combined oral therapy with metformin and glimepiride in the current era. METHODS: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists and diabetologists from India and Nepal. RESULTS: The panel thoroughly reviewed existing literature on the subject and proposed clinical evidence and practice-based guidelines. CONCLUSION: These current clinical practice guidelines highlight the efficacy and safety of basal insulin combination therapy with various available basal insulins including neutral protamine hagedorn, detemir, glargine and degludec in addition to metformin and glimepiride therapy.

Position of Sulfonylureas in the Current ERA: Review of National and International Guidelines.

Sulfonylureas (SUs) are one of the commonly prescribed oral anti-hyperglycemic agents (AHA) in low- and middle-income countries (LMICs), either in combination with metformin therapy or alone. However, concern about cardiovascular safety has limited the use of SUs in the management of type 2 diabetes mellitus (T2DM). Additionally, lack of uniformity in the national and international guidelines regarding the positioning of SUs in the management of diabetes has also been reported. The objective of this review was to assess the various national and international guidelines on diabetes management and understand the recommendations specific to SUs in various scenarios. A total of 33 national and international guidelines on the management of T2DM published in English were evaluated. These guidelines have considered the latest evidence and suggest the use of certain second-generation SUs as second-line therapy or in combination with other AHAs in select population and specific scenarios. Identification of the appropriate population, classification based on underlying risk, thorough assessment of the comorbid conditions, and a step-wise approach for the selection of appropriate SUs is essential for the effective management of T2DM. Additionally, cost-to-benefit ratio should be considered, particularly in LMICs, and SUs could continue to play an important role in such settings.

Insulinization in T2DM with Basal Analogues During COVID-19 Pandemic: Expert Opinion from an Indian Panel.

The ongoing global pandemic of the coronavirus disease 2019 (COVID-19) has placed a severe strain on the management of chronic conditions like diabetes. Optimal glycemic control is always important, but more so in the existing environment of COVID-19. In this context, timely insulinization to achieve optimal glycemic control assumes major significance. However, given the challenges associated with the pandemic like restrictions of movement and access to healthcare resources, a simple and easy way to initiate and optimize insulin therapy in people with uncontrolled diabetes is required. With this premise, a group of clinical experts comprising diabetologists and endocrinologists from India discussed the challenges and potential solutions for insulin initiation, titration, and optimization in type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic and how basal insulin can be a good option in this situation owing to its unique set of advantages like lower risk of hypoglycemia, ease of training, need for less monitoring, better adherence, flexibility of using oral antidiabetic drugs, and improved quality of life compared to other insulin regimens. The panel agreed that the existing challenges should not be a reason to delay insulin initiation in people with uncontrolled T2DM and provided recommendations, which included potential solutions for initiating insulin in the absence or restriction of in-person consultations; the dose of insulin at initiation; the type of insulin preferred for simplified regimen and best practices for optimal titration to achieve glycemic targets during the pandemic. Practical and easily implementable tips for patients and involvement of stakeholders (caregivers and healthcare providers) to facilitate insulin acceptance were also outlined by the expert panel. Simplified and convenient insulin regimens like basal insulin analogues are advised during and following the pandemic in order to achieve glycemic control in people with uncontrolled T2DM.

Expert Group Recommendations on Detection and Management of Hypoglycemia in Routine Clinical Practice in Insulin Treated Patients with Diabetes.

Hypoglycemia is a key barrier to optimum glycemic control in insulin treated diabetes patients. A national level expert group meeting was held at the 11th national insulin summit to analyze published data from clinical studies and guidelines to evolve consensus recommendations on identification and management of hypoglycemia in insulin-treated diabetes patients. This consensus statement emphasizes consideration of suggestive symptoms or blood glucose levels ≤70 mg/dl and ability to self-treat in identification and classification of hypoglycemia. Patient questionnaire administration at each patient visit will enable accurate reporting of hypoglycemia. Patients with strict glycemic control, high glycemic variability, history of severe hypoglycemia, impaired hypoglycemia awareness, long duration of disease or insulin therapy could be at an increased risk of hypoglycemia. Prevention of hypoglycemia should include monitoring and goal setting, patient education, dietary intervention, exercise counseling and medication adjustment. Basal insulin analogues (vs. NPH), rapid-acting insulin analogues (vs. RHI) and premix insulin analogues (vs. BHI) are more appropriate options with superiority of insulin degludec to insulin glargine U100 and IDegAsp to BIAsp 30 to reduce the risk of hypoglycemia. This consensus statement provides practical guidance for physicians in effectively managing and minimizing the risk of hypoglycemia in insulin treated diabetes patients.

Primary hyperparathyroidism: A changing scenario in India.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is largely a symptomatic disease with varied systemic manifestations, complicated by coexisting Vitamin D (Vit D) deficiency. Increasing awareness, developments in diagnostics, and Vit D supplementation may have an impact on the disease profile of PHPT. METHODS: Clinical, biochemical, and pathological profile of PHPT presenting to a tertiary care center in South India were compared in two groups separated as per the period of presentation (Group A: January 1994-May 2007 - 51 cases and Group B: June 2007-January 2015 - 59 cases). RESULTS: PHPT has remained a disease of female preponderance with similar age of presentation. It is being diagnosed earlier (mean duration of symptoms prior to diagnosis was 38.7 months in Group A, significantly longer than 26 months in Group B). Bone pain and metabolic myopathy were the most common presentations (60%) followed by pathological fracture (16%), renal calculi (13%), and pancreatitis (7%). Pathological fractures have become less frequent. Vit D deficiency is still a widespread co-morbidity. Radionuclide scintigraphy is an effective localizing tool, but ultrasound can be an inexpensive and widely available screening modality. CONCLUSION: PHPT still remains asymptomatic disease of bones and stones, although it is being diagnosed early. Greater awareness, Vit D supplementation, and better diagnostic tools have made it a disease with lesser morbidity and effective cure.

Prediction of remission after metabolic surgery using a novel scoring system in type 2 diabetes - a retrospective cohort study.

BACKGROUND: Remission of diabetes is seen in more than 60% of patients after bariatric surgery. There is extensive variability in the remission rates between different surgical procedures. We analyzed our database and aimed to develop an easy scoring system to predict the probability of diabetes remission after two surgical procedures i.e. Ileal Interposition coupled with Sleeve Gastrectomy (IISG) or Diverted Sleeve Gastrectomy (IIDSG). METHODS: In this retrospective study, we analyzed records pertaining to patients who underwent IISG (n = 46) and IIDSG (n = 29). The primary outcome measure was diabetes remission (A1c <6.5% and not requiring hypoglycemic drugs). We identified seven preoperative clinical variables (age, duration of diabetes, body mass index, micro and macrovascular complications, use of insulin and stimulated C-peptide) based on our previous reports to be included in the diabetes remission score (DRS). The DRS score (7 - 14) was compared between the patients with and without remission in both the surgery groups. RESULTS: Mean DRS in patients who underwent IISG was 9.2 ± 1.4. Twenty one (46%) had a remission in diabetes. DRS was significantly lower in patients with remission than patients without remission (8.1 ± 0.8 versus 10.2 ± 0.9, p < 0.0001). Mean DRS in patients who underwent IIDSG was 10.4 ± 1.3. Twenty one (72%) had a remission in diabetes. DRS was significantly lower in patients with remission than patients without remission (9.7 ± 0.8 versus 12.0 ± 0.5, p < 0.0001). Patients with a DRS ≥ 10 in IISG group and more than 12 in IIDSG group did not get into remission. CONCLUSION: Preoperative DRS can be a useful tool to select the type of surgical procedure and to predict the postoperative diabetes remission. TRIAL REGISTRATION: NCT00834626.

A case of Liddle's syndrome; unusual presentation with hypertensive encephalopathy.

Liddle's syndrome is a rare cause of secondary hypertension. Identification of this disorder is important because treatment differs from other forms of hypertension. We report an interesting case of a 35-year-old lady, a known diabetic and hypertensive patient, who presented with features of hypertensive encephalopathy. The family history was unremarkable. Past treatment with various combinations of antihypertensive medications including spironolactone, all at high doses, failed to control her blood pressure. Upon evaluation, the patient had hypokalemic alkalosis, low 24-h urine potassium and suppressed plasma renin activity. Although these findings were similar to hyperaldosteronism, plasma aldosterone was lower than the normal range. Blood pressure decreased markedly after administration of amiloride. Along with hyporeninemic hypo-aldosteronism, the non-responsiveness to spironolactone and good response to amiloride established the diagnosis of Liddle's syndrome.

Metabolic pancreatitis: Etiopathogenesis and management.

Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

Fetal endocrinology.

Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition.

Glycemic variability: Clinical implications.

Glycemic control and its benefits in preventing microvascular diabetic complications are convincingly proved by various prospective trials. Diabetes control and complications trial (DCCT) had reported variable glycated hemoglobin (HbA1C) as a cause of increased microvascular complications in conventional glycemic control group versus intensive one. However, in spite of several indirect evidences, its link with cardiovascular events or macrovascular complications is still not proved. Glycemic variability (GV) is one more tool to explain relation between hyperglycemia and increased cardiovascular risk in diabetic patients. In fact GV along with fasting blood sugar, postprandial blood sugar, HbA1C, and quality of life has been proposed to form glycemic pentad, which needs to be considered in diabetes management. Postprandial spikes in blood glucose as well as hypoglycemic events, both are blamed for increased cardiovascular events in Type 2 diabetics. GV includes both these events and hence minimizing GV can prevent future cardiovascular events. Modern diabetes management modalities including improved sulfonylureas, glucagon like peptide-1 (GLP-1)-based therapy, newer basal insulins, and modern insulin pumps address the issue of GV effectively. This article highlights mechanism, clinical implications, and measures to control GV in clinical practice.

Carotid intima media thickness in type 2 diabetes mellitus with ischemic stroke.

BACKGROUND: Diabetes mellitus is associated with high cardiovascular risk. Carotid intima media thickness (CIMT) is used commonly as a noninvasive test for the assessment of degree of atherosclerosis. The objective of this study was to find out the cut-off point for CIMT for ischemic stroke in patients with type 2 diabetes mellitus (T2DM) and to correlate CIMT with various parameters like smoking, hypertension, lipid profile and duration of T2DM. MATERIALS AND METHODS: A total of 80 subjects in the age group of 30-75 years (M:F = 57:23) were selected and divided into three groups, i.e. diabetes with ischemic stroke, diabetes and healthy subjects. All the participants were subjected to B-mode ultrasonography of both common carotid arteries to determine CIMT, along with history taking, physical examination and routine laboratory investigations including included fasting and 2-hour postprandial blood sugar, blood urea, serum creatinine, lipid profile, glycated hemoglobin, and microalbuminuria. RESULTS: Patients with T2DM with or without ischemic stroke were found to have significantly higher prevalence of increased CIMT and a value greater than 0.8 mm was found to be associated with the occurrence of stroke. The mean carotid IMT of the group as a whole was 0.840 ± 0.2 mm. The mean carotid IMT was not significantly different between T2DM patients with or without ischemic stroke (1.06 ± 0.2 vs. 0.97 ± 0.26 mm, P = 0.08). However, the mean CIMT was significantly higher in diabetic subjects compared to healthy subjects (1.01 ± 0.28 mm vs. 0.73 ± 0.08, P = 0.006). Other parameters like higher age, smoking, hypertension, hyperlipidemia, low HDL cholesterol, the glycemic parameters and the duration of diabetes were independently and significantly related to CIMT. CONCLUSION: A high CIMT is a surrogate and reliable marker of higher risk of ischemic stroke amongst type 2 diabetic patients. Our study demonstrates the utility of carotid IMT as a simple non-invasive screening test for the assessment of atherosclerosis risk/prognosis in type 2 diabetics.

Implications of serum paraoxonase activity in obesity, diabetes mellitus, and dyslipidemia.

Human serum paraoxonase 1 (PON1) is an enzyme with esterase activity, and is physically bound to high-density lipoproteins (HDL). It plays a key role in the action of HDL toward protection of lipoprotein and biological membrane against oxidative damage. It may have a protective role against atherosclerosis by virtue of its action on hydrolyzing lipid peroxides and preventing accumulation of phospholipids in oxidized low-density lipoprotein (LDL). PON1 is hypothesized to be an indicator of the risk of atherosclerosis and coronary artery disease development. Numerous studies have implicated PON1 activity in relation to various endocrine disorders. The current article reviews the clinical perspectives of PON1 activity with regards to obesity, diabetes mellitus with its complications, and dyslipidemia.

Endocrinology of parturition.

The myometrium must remain relatively quiescent during pregnancy to accommodate growth and development of the feto-placental unit, and then must transform into a highly coordinated, strongly contracting organ at the time of labour for successful expulsion of the new born. The control of timing of labour is complex involving interactions between mother, fetus and the placenta. The timely onset of labour and delivery is an important determinant of perinatal outcome. Both preterm birth (delivery before 37 week of gestation) and post term pregnancy (pregnancy continuing beyond 42 weeks) are both associated with a significant increase in perinatal morbidity and mortality. There are multiple paracrine/autocrine events, fetal hormonal changes and overlapping maternal/fetal control mechanisms for the triggering of parturition in women. Our current article reviews the mechanisms for uterine distension and reduced contractions during pregnancy and the parturition cascade responsible for the timely and spontaneous onset of labour at term. It also discusses the mechanisms of preterm labour and post term pregnancy and the clinical implications thereof.

Carbimazole-induced cholestatic hepatitis in Graves' disease.

Antithyroid medications are one of the treatment options for Graves' disease. Carbimazole is widely used as the drug of choice, except in pregnancy, where propythiouracil is preferred by many. It is generally well-tolerated. Its side-effects include allergy, upper gastrointestinal upset, a rare occurrence of granulocytosis, and others. Hepatitis is another rare, but serious side-effect. We report a healthy 30-year-old male patient with Graves' disease, who developed cholestatic jaundice after Carbimazole therapy for four months. He made a full recovery after the drug was discontinued. An idiosyncratic mechanism seemed likely.

Aberrant angiogenesis: The gateway to diabetic complications.

Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes.

Coexistence of pheochromocytoma with uncommon vascular lesions.

BACKGROUND: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. MATERIALS AND METHODS: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. RESULTS: Of the 50 patients with pheochromocytoma, 7 (14%) had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. CONCLUSION: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis.

ACE inhibitors or ARBs for diabetic nephropathy: the unrelenting debate.

Adequate control of blood pressure is of paramount importance in delaying the progression of renal disease in diabetic patients. Drugs acting on renin angiotensin aldosterone axis are of proven value in diabetes. Particularly angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have benefits beyond blood pressure control. The current article focuses on various studies supporting the use of ACEIs and ARBs in diabetic subjects.

Clinical profile of coexisting conditions in type 1 diabetes mellitus patients.

AIMS: Type 1 diabetes mellitus (T1DM) is associated with various genetic and autoimmune diseases implicated in its etiopathogenesis. We hereby profile the clinical association of such diseases among patients from our center. METHODS: Consecutive patients of T1DM presenting to department of Endocrinology from May 1997 to December 2011 were retrospectively analyzed in context of associated clinical profile. RESULTS: Among 260 patients diagnosed as T1DM, 21 (8%) had hypothyroidism, 4 (1.5%) had hyperthyroidism and 2 (0.7%) had primary adrenal insufficiency. Eighteen patients (7%) had celiac disease, 9 (3.5%) had Turner's syndrome, 5 patients (1.9%) had Klinefelter's syndrome, whereas Down's syndrome and Noonan's syndrome was present in 2 and 1 patients (0.7%) respectively. One patient had Wolframs' syndrome and 1 patients had myasthenia gravis. Systemic lupus erythematosus and rheumatoid arthritis were present in 3 and 1 patients respectively. Total of 5 patients with cerebral palsy, 4 cases with deaf mutism, 4 cases with acute psychosis and 16 patients with depression were noted. Mean age of study patients was 20.8±9.8 years (range, 3-23 years). CONCLUSION: Various conditions including genetic (Down, Turner, Noonan, and Klinefelter's), autoimmune (thyroid and adrenal disorders, myasthenia gravis, SLE, rheumatoid arthritis) and central nervous system diseases were the associated diseases encountered in our patients. Routine screening is required for early diagnosis and treatment of associated co morbidities.