Vimal Upreti

Efficacy of Autologous Bone Marrow–Derived Stem Cell Transplantation in Patients With Type 2 Diabetes Mellitus

Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and beta-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (> or = 0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by > or = 50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement (r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group (P = 0.03) and responders (P = 0.03). HOMA-B increased significantly in the whole group (P = 0.02) and responders (P = 0.04) whereas, HOMA-IR did not change significantly (P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline (r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells (r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.

Spectrum of neurological manifestations of idiopathic hypoparathyroidism and pseudohypoparathyroidism.

We describe clinical, biochemical, radiological profile, and treatment outcome in 97 patients with idiopathic hypoparathyroidism seen over a period of 18 years. Of the 97 patients, 78 (80%) had idiopathic hypoparathyroidism and 19 (20%) had pseudohypoparathyroidism. The mean age±standard deviation (SD) at presentation was 28.7±14.1 years. There were 52 males, the mean lag time from first reported symptom to diagnosis was 5.9±5.2 years and the mean (±SD) follow-up was 1.8±0.4 years. The most common presenting manifestation was carpopedal spasm in 68 (70%) patients, followed by paresthesia and seizures in 52 (54%) patients. The mean (±SD) serum calcium and inorganic phosphate concentrations were 6.1±1.5 mg/dl and 6.3±1.5 mg/dl, respectively. The most common imaging abnormality noted was basal ganglia calcification followed by cerebral cortex and cerebellum calcification. More than one-third of patients were on various antiepileptic drugs including phenytoin. In addition to oral calcium and active vitamin D (calcitriol), twenty-six patients (27%) also required hydrochlorothiazide. The important finding in our study was long lag time from the first reported symptom to diagnosis. Phenytoin was the drug in almost one- third of our patients with seizures. Practicing clinicians should have high index of suspicion of diagnosis hypoparathyroidism in the appropriate clinical states to avoid the morbidity associated with hypoparathyroidism. Phenytoin should be avoided in patients with hypoparathyroidism and seizures.

Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study.

Background: there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT) through targeted approach in Type 2 Diabetes Mellitus. This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM. Materials and Methods: Ten patients (8 men and 2 women) with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day), metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance. The primary outcome measure was decrease in insulin requirement by ≥50% (defined as responders), while secondary endpoints were improvement in glucagon stimulated C-peptide levels, changes in weight, HbA1c, lipid profile and quality of life (QOL) at the end of 15 months. Results: Six patients (60%) were ‘responders’ at 15 months of follow-up showing a reduction in mean insulin requirement by 74% as compared to baseline and one patient was off-insulin till the end of the study. Mean HbA1c reduction in ‘responders’ was 1.1% (8.1 ± 0.5% to 7.0 ± 0.6%, P = 0.03), accompanied with a significant improvement in glucagon stimulated C-peptide levels (P = 0.03), Homeostasis Model Assessment -β (P = 0.03) and QOL scores. However, ‘non-responders’ did not show any significant alterations in these parameters. No serious adverse events were noted. Conclusion: Our observations indicate that ABMSCT is effective in management of T2DM and its efficacy is maintained over a period of 15 months without any adverse events. However, more number of patients and longer duration of follow-up are required to substantiate these observations.

Botulinum toxin for meralgia paresthetica in type 2 diabetes

Botulinum toxin has been used for a variety of neuropathic conditions in diabetes mellitus. Meralgia paresthetica is a mononeuropathy of femoral nerve seen in diabetes and obesity with an unclear etiopathogenesis. We studied the role of botulinum toxin in resistant cases of meralgia paresthetica in type 2 diabetes.

Comparison of thrice daily biphasic human insulin (30/70) versus basal detemir & bolus aspart in patients with poorly controlled type 2 diabetes mellitus - A pilot study

Background & objectives: Conventionally, biphasic human insulin (30/70, BHI) is used twice daily for the management of patients with diabetes. However, this regimen is suboptimal to control post-lunch and/or pre-dinner hyperglycaemia in some patients. This study was undertaken to compare the efficacy and safety of thrice-daily biphasic human insulin (30/70, BHI) versus basal detemir and bolus aspart (BB) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Methods: In this open labelled randomized pilot study, 50 patients with uncontrolled T2DM on twice-daily BHI and insulin sensitizers were randomized either to BHI thrice-daily or BB regimen. HbA1c, six point plasma glucose profile, increment in insulin dose, weight gain, hypoglycaemic episodes and cost were compared between the two treatment groups at the end of 12 wk. Results: Mean HbAlc (±SD) decreased from 9.0±0.9 per cent at randomization to 7.9±0.8 per cent in BHI (P<0.001) and from 9.4±1.3 to 8.2±1.0 per cent in BB regimen (P<0.001) after 12 wk of treatment. The mean (±SEM) weight gain in patients in the BHI regimen was 1.5±0.33 kg compared to 1.4±0.34 kg in the BB regimen. Insulin dose increment at 12 wk was significantly more in the BB regimen 0.46±0.32 U/kg/day compared to 0.15±0.21 U/kg/day in the BHI regimen (P<0.001). The incidence of major as well as minor hypoglycaemic episodes was not different in both the regimen. The BB regimen was more expensive than the BHI regimen (P<0.001). Interpretation & conclusions: The thrice daily biphasic human insulin regimen is non-inferior to the basal bolus insulin analogue regimen in terms efficacy and safety in patients with poorly controlled T2DM. However, these data require further substantiation in large long term prospective studies.

An uncommon cause of recurrent pyogenic meningitis: pituitary abscess.

The authors report a 36-year-old male who presented with headache and hypopituitarism, and MRI revealed a ring enhancing lesion with pituitary stalk thickening. During follow-up, he presented with recurrent pyogenic meningitis with persistence of the lesion, therefore a diagnosis of pituitary abscess was considered. He underwent trans-sphenoidal surgery (TSS) with evacuation of pus and received antibiotic treatment for the same. After this he remarkably improved and had no recurrence of symptoms. He is on levothyroxine, glucocorticoids and testosterone replacement therapy for his respective hormone deficits.

Efficacy of teriparatide in patients with hypoparathyroidism: A prospective, open-label study

Context: Conventional treatment of hypoparathyroidism with calcium, Vitamin D analogs, and thiazide diuretics is often suboptimal, and these patients have poor quality of life. Teriparatide (parathyroid hormone 1–34 [PTH (1–34)]), an amide of PTH, is widely available for the use in osteoporosis; however, its use in hypoparathyroidism is limited. Aims: The aim of this study is to evaluate the efficacy of PTH (1–34) in the treatment of patients with hypoparathyroidism. Settings and Design: This was a prospective, open-label interventional study in a tertiary care hospital of Indian Armed Forces. Subjects and Methods: All patients with hypoparathyroidism presented to the endocrinology outpatient department were included and were exhibited injection PTH (1–34) 20 μg twice daily that was gradually reduced to 10 μg twice daily along with calcium, active Vitamin D (alfacalcidol), and hydrochlorothiazide. Oral calcium and alfacalcidol doses were also reduced to maintain serum calcium within normal range. The quality of life (QOL) score was calculated using RAND 36 QOL questionnaire at baseline and termination of the study. Statistical Analysis Used: Paired t-test was used to calculate pre- and post-treatment variables. Results: Eight patients (two males) were included in this study having mean age of 35.8 years. PTH (1–34) treatment led to the improvement in serum calcium (6.81–8.84 mg/dl), phosphorous (5.8–4.2 mg/dl), and 24 h urinary calcium excretion (416–203.6 mg). Parameters of QOL showed the improvement in overall QOL, physical performance, energy, and fatigue scores. No major adverse events were noted. Conclusions: Treatment of hypoparathyroidism with PTH (1–34) leads to improvement in calcium profile, reduction in hypercalciuria, and improvement in QOL, whereas it is safe and well tolerated.

Etiopathological differentiation of diabetes mellitus in lean, young adults

OBJECTIVE Classification of diabetes mellitus (DM) into type 1 or type 2 is difficult in lean, young individuals. We studied the β-cell function, insulin resistance (IR) and autoimmunity in young patients with recent onset DM. METHODS In this cross-sectional study, we included patients (age below 35 years) with recent onset DM (<6 months) and normal body weight for evaluation. The detailed clinical examination was done to identify markers of IR. Autoimmune DM was diagnosed using glutamic acid decarboxylase 65 (GAD65), insulin autoantibody (IAA) and islet cell antibody (ICA). Homeostasis model assessment (HOMA) models of HOMA-B and HOMA- IR were used for estimation of β-cell function and IR respectively. The patients were divided into four groups based on, the autoimmunity (A) and ketosis (K) as group 1 (A+K), group 2 (A-K+), group 3 (A+K-) and group 4 (A-K-). Appropriate statistical tests +)were used to analyze the results. RESULTS The study population (n=75, all males) had a mean age of 28.9±4.3years, body mass index 20.6±1.9kg/m2, fasting plasma glucose 177.1±31.4mg/dl and HbA1c of 9.9±2.1% at presentation. The number of patients in groups 1 to 4 are 8, 5, 10 and 52 respectively (p<0.0001). HOMA-IR was higher in groups 2 and 4 (4.1±1.3, 3.6±1.1 respectively), whereas HOMA-B was higher in group 4 (3.6±1.5) alone (p=0.0005). CONCLUSION Type 2 DM is the most common etiology even in young, lean adults in India. Further studies with large numbers are required to confirm our findings.

Prayer sign in diabetes mellitus.

Indian Journal of Endocrinology and Metabolism / Jul-Aug 2013 / Vol 17 | Issue 4 769 when they felt their health had improved). There were also shortcomings in how information was distributed to the patients, because people did not know where to get help, what services are available. It appeared that general practitioners were not always able to diagnose rheumatism early enough. We showed that training courses would be needed for support persons, and family members as well. Based on these fi ndings, we made suggestions at the level of state, doctors and patients. We emphasised the need for continuing such sociological studies, including qualitative and mixed methods research. As our reviewers stated, it is often the patients who know the answer to how their situation could be improved.

Shock due to amlodipine overdose

Amlodipine is a commonly prescribed calcium channel blocker. Its toxicity is the leading cause of drug overdose seen in the practice of cardiovascular medicine. It can lead to profound hypotension and shock. Management involves early and aggressive supportive measures and calcium infusion in large doses to overcome competitive blockade. We report one such case that presented with amlodipine overdose and was successfully managed.