Evolution of Guideline Recommendations on Insulin Therapy in Type 2 Diabetes Mellitus Over the Last Two Decades: A Narrative Review.

The prevalence of type 2 diabetes mellitus has been increasing worldwide. As the therapeutic options for type 2 diabetes mellitus have evolved over the last 2 decades, national and global guidelines related to type 2 diabetes mellitus pharmacotherapy issued by various organizations have tended to vary in their recommendations. This narrative review aimed to analyze the key recommendations by major global and national guidelines on the initiation of insulin therapy in patients with type 2 diabetes mellitus over the last 20 years. Strategies for insulin therapy for titration and intensification were also assessed. All guidelines recommend initiation of insulin (basal/ premixed/other formulations) when glycemic targets are not achieved despite lifestyle measures and oral antidiabetic drugs. In the recent decade, early initiation of insulin has been recommended when the glycated hemoglobin levels are >10% or blood glucose levels are ≥300 mg/dL (16.7 mmol/L). Initiation is recommended at a dose of 10 units or 0.1-0.2 U/kg. Titration is advised to achieve the optimal dosage, while intensification is recommended when glycemic targets are not achieved despite titrating to an acceptable level. Glucose monitoring at periodic intervals is recommended for adequate glycemic control. The guidelines further suggest that the choice of insulin should be individualized, considering the clinical status of patients with type 2 diabetes mellitus. The physicians as well as patients should be a part of the decisions made regarding the therapeutic choice of regimen, preparation, and delivery device.

Prameha purvaroopa as diabetes risk predictor - trends from a retrospective cohort study of newly diagnosed type 2 diabetes patients.

STUDY BACKGROUND: Increasing prevalence of type 2 diabetes has shifted the focus of world from its management to prevention. Life style modifications programs related to diabetes prevention are found to delay the progress of prediabetes into diabetes. Reaching out to community with diabetes prevention program however is still a challenge to meet. OBJECTIVE: Of the study: This study proposed to retrospectively screen the presence of prediabetes symptoms depicted in Ayurveda literature in a newly diagnosed diabetic population and to compare this prevalence with non-diabetic and healthy population. The idea is to put weightage upon prediabetes symptoms as a disease predictor if these are available early in the course of the disease. MATERIAL AND METHODS: A questionnaire based upon detailed literature survey of three Ayurveda classics from the subject area of prameha (identical to diabetes) identified 22 features under the class of prediabetes. A questionnaire was developed to find the presence of these features in selected diabetic population retrospectively before the onset of diabetes. 141 newly diagnosed diabetics were selected on the basis of a defined inclusion and exclusion criteria and surveyed for chronological presence of prediabetes features as identified through the literature search and validated through a validation process. This feature prevalence was further compared with non-diabetic and healthy population. RESULTS: A significant difference (p < 0.001) was observed in specific symptom occurrence in diabetic population comparing to non-diabetic and healthy control for at least 11 of the selected items. CONCLUSION: The study observes that few prediabetes features show their clear retrospective presence in diabetic population comparing to non-diabetic and healthy population. This observation can help formulating a risk calculator for future diabetes on the basis of available pre diabetic features in an individual. A prospective cohort study however would be essential to prove any such realistic relation between prediabetes symptoms and future diabetes development among high risk individuals.

Predicting and preventing diabetes: Translational potential of Ayurveda information on pre-diabetes.

Continued rise in incidence and prevalence of diabetes globally warrants an effective strategy for its prevention and control. Prevention of diabetes seems more logical to attempt seeing its health care burden, long dormancy, systemic affliction and poor general awareness. Pre-diabetes is the intermediate state of erratic glucose metabolism without overt features of diabetes. This state seems to be a crossroad having a possibility to either convert into clinical diabetes, remain dormant or return to normal glucose control depending upon the efforts made. Unfortunately, due to the paucity of apparent clinical symptoms, this state embedded with reversal possibility, remains unexplored. Ayurveda account of prameha purvarupa (subclinical features of diabetes) may be proposed as the foundation upon which clinic-based pre-diabetes identification and subsequent prevention may be explored. Knowing the symptoms for their reliable proximity with upcoming diabetes may turn to be sensible sensitizers prompting the people to abort the disease process in an effective and timely manner. Considering diabetes from its purvarupa to complications as disease continuum and exploring the opportunities to intervene in order to prevent, or manage the disease on the basis of shada kriyaa kaala therefore, has a huge translational potential warrants an urgent exploration.

High resolution ultrasonography of peripheral nerves in diabetic patients to evaluate nerve cross sectional area with clinical profile.

OBJECTIVES: The aim of this observational study was ultrasound evaluation of peripheral nerves cross-sectional area (CSA) in subjects with probable diabetic peripheral sensorimotor neuropathy (DPN). CSA was analyzed with reference to clinical and nerve conduction study's (NCS) parameters for early diagnosis and pattern of involvement. METHODS: A total of 50 patients with probable DPN due to Type 2 diabetes and 50 age-matched healthy controls underwent sonographic examinations of ulnar nerve at the lower arm, median nerve proximal to carpal tunnel, the common peroneal nerve proximal to fibular head, tibial nerve proximal to the tarsal tunnel, and sural nerve at lower third leg. RESULTS: CSA was increased in cases of DPN as compared to healthy controls. Area changes were more marked with demyelinating pattern. Probable DPN cases with normal NCS had significantly higher number of peripheral nerves showing increased CSA as compared to healthy control. A cut-off of >4 nerve thickening showed a sensitivity of 86 %, and specificity of 56%. The neuropathy pattern in the lower limb was axonal, whereas in the upper limb, it was demyelinating with the majority showing sonographic feature of associated compressive neuropathy. CONCLUSION: There is an increase in CSA of peripheral nerve in diabetic patients. It can be used as a morphological marker for classifying DPN with changes being picked up earlier to NCS abnormality. Clinical neurological presentation in probable DPN can also be due to compressive neuropathy in early phases, and ultrasound can be a useful tool. ADVANCES IN KNOWLEDGE: Early pick up of DPN cases shall be useful for early therapy and motivating the patients to actively participate in the treatment. Morphological changes on ultrasonography precedes the electrodiagnostic change in DPN. Symptoms of DPN is not only due to metabolic changes but also compressive neuropathy.

Advanced Magnetic Resonance Imaging Techniques in Tuberculous Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is a highly devastating manifestation of tuberculosis. So far, the major role of the neuroradiology in the management of TBM has been restricted to diagnosis and follow-up of the complications. This study aimed to establish the use of advanced magnetic resonance imaging (MRI) techniques in the early detection of sequelae of TBM like vasculitis and hydrocephalous. MATERIALS AND METHODS: In this prospective observational study, 30 patients of TBM were recruited during 1 year at a tertiary care health center of northern India and their serial MRI brain was done. Patients were between 18 and 45 years of age. RESULTS: Basal/Sylvian exudates were seen in 90% of patients, hydrocephalus was found in 30% of patients and infarcts were found in 27% of patients. No significant difference was found between the mean, mean diffusivity (MD), and mean fractional anisotropy (FA) in frontal white matter, basal ganglia, thalamus, pons of cases and controls. A significant difference was seen between mean cerebral blood flow (CBF) in the region of basal ganglia of cases and controls (P < 0.05). No significant difference was seen between mean CBF in frontal white matter, thalamus of cases and controls. Diffusion tensor imaging parameters, MD, and FA were abnormal in the region of infarcts (basal ganglia) in three patients in the first scan, the parameters normalized in one patient (late subacute to chronic infarct in the first scan), and they remained abnormal in two patients. CONCLUSION: Advanced MRI techniques (magnetization transfer imaging) is helpful in visualizing hyperintense thickened meninges in basal cisterns and Sylvian fissures on pre-contrast imaging, and in identifying reduced CBF in the region of basal ganglia.

Nonlinear parameter of heart rate variability can diagnose early cardiac autonomic neuropathy.

This is a case of a 63-year-old female presenting with diabetes mellitus, hypertension, hypothyroidism, and postmenopausal osteoporosis with findings showing abnormal AFT with reduced heart rate variability (HRV) and multiple lobed Poincaré plot, pointing to premature atrial contractions.

Vitamin D Status in Infants during the First 9 Months of Age and its Effect on Growth and Other Biochemical Markers: A Prospective Cohort Study.

BACKGROUND: Despite food fortification policies in many countries and recommendations for Vitamin D supplementation of at-risk groups, Vitamin D deficiency (VDD) and infantile rickets remain major public health challenges in many developed and developing countries. MATERIALS AND METHODS: Ninety-six participants at birth were enrolled and followed up until 9 months of age. Serum 25OHD was estimated in cord blood at birth and at 14 ± 1 weeks of life. Seventy-seven participants were followed up at 9 months for estimation of serum 25OHD, parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium, and phosphorus. VDD was defined as serum 25OHD <15 ng/mL as per USIOM guidelines. RESULTS: Serum 25OHD levels at 9 months of age (15.78 ± 8.97 ng/mL) were significantly increased in comparison to the level of 3 months of age (14.04 ± 7.10 ng/mL) and at birth (8.94 ± 2.24 ng/mL). At birth, all the participants (77) were deficient in 25OHD levels. It was found that 16/94 (17%) and 19/77 (24.7%) participants at 3 and 9 months of age, respectively, became Vitamin D sufficient without any Vitamin D supplementation. There was a significant inverse correlation between serum 25OHD and PTH concentration (r = -0.522, P < 0.001), serum 25OHD and ALP (r = -0.501, P < 0.001). It was found that reduction in serum Vitamin D level to <10.25 ng/mL results in a surge of serum PTH. CONCLUSION: VDD is common from birth to 9 months of age but incidence decreases spontaneously even without supplementation. Furthermore, a large number of babies may be falsely labeled as Vitamin D deficient with currently followed cutoffs. Hence a new cutoff for VDD needs to be established for neonates and infants.

Prognostic Value of Thyroid Profile in Critical Care Condition.

BACKGROUND: Patients suffering from critical illness admitted to the Intensive Care Unit (ICU) exhibit alterations in their thyroid hormone levels, collectively termed as euthyroid sick syndrome or nonthyroidal illness syndrome. Our study was conducted to determine the correlation between these changes in thyroid hormone levels and the prognosis of ICU-admitted patients. METHODS: A total of 270 ICU-admitted patients without previous history of thyroid disorder were included in the study. We recorded their baseline characteristics, acute physiology and chronic health evaluation (APACHE-II) score, thyroid hormone levels, lactate, and other parameters on admission. ICU mortality was the primary outcome. We analyzed the ability of each parameter to predict mortality in the participants. Further, we also evaluated whether the combination of thyroid hormone levels with APACHE-II score could improve the mortality prediction. RESULTS: The mean age of the study population was 38.99 ± 18.32 years. A total of 81 patients (30%) expired during their ICU treatment. Both fT3 and fT4 levels were lower in nonsurvivors compared to survivors. Among the thyroid hormones, fT3 had the highest predictive value for ICU mortality, as seen by the largest area under the curve (AUC) value (0.990 ± 0.007) which was even greater than AUC of APACHE-II score (0.824 ± 0.051) and fT4 (0.917 ± 0.049). Univariate logistic regression analysis showed that fT3 (ß = 140.560) had the highest predictive potential for ICU mortality compared with APACHE-II score (ß = 0.776), fT4 (ß = 17.62) and other parameters. Multivariate logistic regression analysis revealed that the combination of fT3 and APACHE-II (R2 = 0.652) was superior in predicting mortality than APACHE-II alone (R2 = 0.286). CONCLUSION: We observed that fT3 was the strongest predictor of ICU mortality compared to all other parameters included in our study. Further, the combination of fT3 levels and APACHE-II scores provided for a higher probability for predicting mortality in ICU patients.

Gemigliptin: Newer Promising Gliptin for Type 2 Diabetes Mellitus.

The dipeptidyl peptidase-4 (DPP-4) inhibitors have facilitated the management of type 2 diabetes mellitus (T2DM) owing to their superior efficacy and safety with low incidence of adverse effects. Gemigliptin is a new member of this family of drugs, and studies have revealed certain advantages of gemigliptin use compared to its previous congeners. Besides, this drug has also been studied for the treatment of T2DM as monotherapy, in combination with metformin or other oral antidiabetic drugs and in T2DM with moderate-to-severe renal failure. In this review, we explore the published data highlighting the pharmacology, efficacy, and safety of gemigliptin along with its recommendations for use in patients with T2DM.

Hashimoto's Encephalitis: Rare Manifestation of Hypothyroidism.

Hashimoto's encephalitis is a rare, heterogeneous and completely treatable form of neuroendocrine disorder manifesting with seizures, stroke-like episodes, encephalopathy, dementia and variable neuropsychiatric manifestations. It is generally associated with a background of Hashimoto's Thyroiditis, and the patient has high titers of antithyroid antibodies, especially antithyroid peroxidase antibodies. This entity responds dramatically to corticosteroids, hence should be always considered and excluded while treating a patient with encephalopathy in the background of a thyroid disease.

Thyroid functions and serum lipid profile in metabolic syndrome.

BACKGROUND: Thyroid hormones are known to affect energy metabolism. Many patients of metabolic syndrome have subclinical or clinical hypothyroidism and vice versa. To study the correlation of thyroid profile and serum lipid profile with metabolic syndrome. METHOD: It is a hospital based cross sectional case-control study carried out in tertiary care health center, we studied thyroid functions test and serum lipid profile in 100 metabolic syndrome patients according to IDF criteria and a similar number of age, gender and ethnicity matched healthy controls. RESULT: We found that serum HDL was significantly lower (p < 0.001) in cases (41.28 ± 8.81) as compared to controls (54.00 ± 6.31). It was also found that serum LDL, VLDL, triglyceride levels and total cholesterol were found to be significantly higher (p < 0.001) in cases than controls. Serum TSH levels of subjects in cases group (3.33 ± 0.78) were significantly higher (p < 0.001) than that of controls (2.30 ± 0.91) and significantly lower levels of T4 (p < 0.001) in the patients of metabolic syndrome (117.45) than in controls (134.64) while higher levels of T3, although statistically insignificant in the patients of metabolic syndrome. CONCLUSION: Thyroid hormones up-regulate metabolic pathways relevant to resting energy expenditure, hence, obesity and thyroid functions are often correlated.

Van Wyk-Grumbach Syndrome with Kocher-Debré-Sémélaigne Syndrome: Case Report of a Rare Association.

BACKGROUND: Van Wyk-Grumbach syndrome (VWGS) is a rare presentation of juvenile hypothyroidism which manifests in females as chronic autoimmune hypothyroidism, isosexual pseudoprecocious puberty, and multicystic ovaries. It uniquely presents with short stature and delayed bone age unlike other causes of precocious puberty. Kocher-Debré-Sémélaigne (KDSS) is a rare presentation of juvenile hypothyroidism manifesting as calf muscle pseudohypertrophy, delayed contraction and relaxation of reflexes, and percussion myxedema. OBJECTIVES: To diagnose the rare association of VWGS and KDSS and to conduct a follow-up of the patient on replacement therapy. METHODS: We present a case of a 9-year-old female child who presented to the endocrine department with complaints of intermittent vaginal bleeding, short stature, and difficulty in walking. On evaluation she was found to be having autoimmune hypothyroidism, FSH-dominated isosexual pseudoprecocious puberty, delayed bone age, secondary pituitary macroadenoma, delayed relaxation of deep tendon reflexes, and pseudohypertrophy of calf muscles. The diagnosis of VWGS associated with KDSS was made. The patient was initially put on 25 µg thyroxine replacement, which was titrated accordingly, and was followed up after 6 months and 1 year. RESULTS: All the features of the syndrome improved after 12 months of adequate thyroxine replacement. CONCLUSIONS: VWGS and KDSS are rare presentations of juvenile hypothyroidism, and their association is even rarer. Early diagnosis and prompt replacement therapy can avoid unnecessary investigations and surgical interventions.

Macroglossia: An Uncommon Manifestation of Primary Hypothyroidism due to Hashimoto's Thyroiditis in a Teenage Child.

Thyroid disorders are prevalent in the paediatric population and untreated hypothyroidism leads to several adverse consequences like mental retardation, neurological impairment, short stature, delayed puberty and increased morbidity. Owing to a wide range of non-specific clinical manifestations, one must have a high index of suspicion for timely diagnosis and treatment of primary hypothyroidism. We describe the case of an adolescent girl who presented with short stature, delayed puberty and feeding difficulties owing to undiagnosed and subsequently untreated hypothyroidism.

Unusual Manifestations Associated with Primary Hypothyroidism: Experience from A Tertiary Care Health Center.

Hypothyroidism is a commonly diagnosed endocrine disorder. Typical signs and symptoms of hypothyroidism include lethargy, cold intolerance, hoarseness, dry skin, constipation, delayed relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may present with unusual signs and symptoms of hypothyroidism which can result in diagnostic confusion. Besides the usual clinical manifestations of primary hypothyroidism, some signs are very unusual and not commonly recorded. The treating physician may not be familiar with them. Hence, timely identification of these unusual presentations is very important for early intervention and treatment.

Prognostic Factors in Patients Hospitalized with Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is characterized by a biochemical triad of hyperglycemia, acidosis, and ketonemia. This condition is life-threatening despite improvements in diabetic care. The purpose of this study was to evaluate the clinical and biochemical prognostic markers of DKA. We assessed correlations in prognostic markers with DKA-associated morbidity and mortality. METHODS: Two hundred and seventy patients that were hospitalized with DKA over a period of 2 years were evaluated clinically and by laboratory tests. Serial assays of serum electrolytes, glucose, and blood pH were performed, and clinical outcome was noted as either discharged to home or death. RESULTS: The analysis indicated that significant predictors included sex, history of type 1 diabetes mellitus or type 2 diabetes mellitus, systolic blood pressure, diastolic blood pressure, total leukocyte count, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, blood urea nitrogen, serum creatinine, serum magnesium, serum phosphate, serum osmolality, serum glutamic oxaloacetic transaminases, serum glutamic pyruvic transaminases, serum albumin, which were further regressed and subjected to multivariate logistic regression (MLR) analysis. The MLR analysis indicated that males were 7.93 times more likely to have favorable outcome compared with female patients (odds ratio, 7.93; 95% confidence interval, 3.99 to 13.51), while decreases in mean APACHE II score (14.83) and serum phosphate (4.38) at presentation may lead to 2.86- and 2.71-fold better outcomes, respectively, compared with higher levels (APACHE II score, 25.00; serum phosphate, 6.04). CONCLUSION: Sex, baseline biochemical parameters such as APACHE II score, and phosphate level were important predictors of the DKA-associated mortality.

Cerebrotendinous xanthomatosis (a rare lipid storage disorder): a case report.

BACKGROUND: Cerebrotendinous xanthomatosis is a very rare autosomal recessive lipid storage disorder affecting bile acid biosynthesis. It is manifested by subtle neurological and non-neurological symptoms due to abnormal tissue lipid deposition. Diagnosis is usually delayed but early diagnosis and replacement therapy can prevent devastating neurological sequelae. CASE PRESENTATION: We present a case of a 25-year-old Asian Indian woman who presented with gait difficulty, fusiform swellings of bilateral tendo-Achilles and infrapatellar tendons, along with history of bilateral cataract surgery 1 year earlier. The diagnosis was made on the basis of clinical, biochemical, imaging, and histopathological analysis and replacement therapy was started. CONCLUSIONS: The peculiarity of the present case is the absence of any neurological manifestations which are usually the early clues to the diagnosis of cerebrotendinous xanthomatosis. The present case report emphasizes the fact that early age bilateral cataracts along with bilateral tendo-Achilles xanthomas can be early pointers toward the diagnosis of cerebrotendinous xanthomatosis.

Turner syndrome with pseudohypoparathyroidism: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;">The association of Pseudohypoparathyroidism (PHP) with Turner syndrome is very rare and only a single case has been reported so far. Both manifest with short stature and lack of secondary sexual characteristics along with other stigmata similar to each other, creating a diagnostic dilemma.<br />We describe a case of a 15-year-old Asian Indian female who presented with short stature and delayed puberty with overlapping phenotype of PHP and Turner syndrome. The diagnosis of Turner syndrome was made easily on the basis of typical history, clinical features and karyotype but the diagnosis of PHP was suspected only after radiological and biochemical investigations. The association of Turner syndrome with PHP can be easily missed due to similar phenotypes and subtle manifestations.</p>