Effect of a multicomponent intervention on achievement and improvements in quality-of-care indices among people with Type 2 diabetes in South Asia: the CARRS trial.

AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.

Evidence of higher intramyocellular fat among normal and overweight Indians with prediabetes.

BACKGROUND: The rise in prevalence rates of Type 2 Diabetes among Indians is well recognized. The research focus has been primarily to understand the changes in insulin sensitivity and beta cell dysfunction among Indians with Type 2 Diabetes. However, no data are available on the role of peripheral tissue, in particular intramyocellular lipid (IMCL) content and its impact on glucose homeostasis among Indians with prediabetes. METHODS: 28 male subjects (20-40 year) were studied. 13 with prediabetes (BMI ranging from 25.4 ± 2.9 kg/m2) and 15 controls (BMI ranging from 24.6 ± 2.8 kg/m2) were recruited. Body composition by dual energy X-ray absorptiometry (DXA), insulin sensitivity, insulin secretion rates were derived using the minimal model of C-peptide secretion and kinetics rates and skeletal muscle strength of the lower limb (quadriceps) was assessed using Isokinetic dynamometry. From muscle biopsy samples of the vastus lateralis, IMCL fat content (Oil red O staining) was determined. RESULTS: The prediabetes group were older compared to controls (P < 0.01), but had similar BMI. The muscle to fat ratio, plasma Insulin, C peptide, HOMA-IR and HOMA % B were also comparable between the groups. IMCL fat content (%) was significantly higher in the prediabetes group compared to controls (7.0 ± 0.7% vs. 2.0 ± 0.3%, P < 0.01). This difference persisted even after controlling for age. Overall the IMCL fat content (%) was positively and significantly associated with HbA1c (r = 0.76, P < 0.01). HOMA-IR was significantly correlated with central (android, trunk) adiposity (kg) (r = 0.71, P < 0.01) but not with IMCL (%). CONCLUSIONS: This is the first direct evidence of existence of significantly higher lipid levels within skeletal muscle cells among normal and overweight young Indians with prediabetes. However, there was no association between IMCL and HOMA-IR among the prediabetes group.

The Role of Circulating MicroRNA in the Regulation of Beta Cell Function and Insulin Resistance among Indians with Type 2 Diabetes.

BACKGROUND: Circulating microRNA (miRNA/miR) levels are emerging out as markers of tissue level changes; however, their role in type 2 diabetes (T2D) needs to be explored. The study aimed to compare the circulating levels of the miRNA (miR9, miR30d, miR1, miR133a, miR29a, miR143) between T2D and gender matched controls and also to evaluate the strength of association between circulating miRNAs and beta cell function/insulin resistance among Indians with T2D. SUBJECTS AND METHODS: Thirty T2D (25-60 years) and their gender matched controls (n = 30) were recruited. Plasma glucose and insulin, HbA1c, lipid profile, and miRNA levels were estimated. Insulin resistance and beta cell function (HOMA IR and %B) were derived. Body composition was assessed by Dual-energy-x-ray absorptiometry (DXA). Comparison between the study groups was performed using independent "t" test and strength of association by Pearson's correlation. RESULTS: There was a significant difference in HOMA IR (P = 0.03) and %B (P = 0.001) between the two study groups. The muscle mass, percent body fat, and muscle to fat ratio were comparable between the two study groups. miRNA 30d was significantly higher in the T2D compared to control group even after controlling for age (P = 0.005). There was a significant positive association between miR30d with HOMA-IR (r = 0.26, P = 0.04). CONCLUSION: The current study demonstrated that miR30d (insulin gene transcription in pancreatic beta cell and regulator of insulin sensitivity in skeletal muscle) was overexpressed among T2D. Further role of other miRNA and their interaction in regulation of beta cell function and insulin resistance needs to be studied.

Comparison of insulin degludec with insulin detemir in type 1 diabetes: a 1-year treat-to-target trial.

The long-term safety and tolerability of insulin degludec (IDeg) was compared with that of insulin detemir (IDet), as basal treatment in participants with type 1 diabetes mellitus (T1DM). In the present multinational, 26-week core + 26-week extension, controlled, open-label, parallel-group trial, adults with T1DM were randomized to IDeg or IDet as basal insulin treatment combined with meal-time bolus insulin aspart. IDeg was administered once daily, whilst IDet was administered once or twice daily depending on patients' glycaemic control. After 1 year, IDeg provided a 33% lower rate of nocturnal hypoglycaemia compared with IDet: estimated rate ratio (IDeg : IDet) 0.67 [95% confidence interval (CI) 0.51; 0.88]; p < 0.05. IDeg improved glycated haemoglobin after 1 year of treatment, similarly to IDet, but IDeg also provided a significantly greater reduction in fasting plasma glucose compared with IDet: estimated difference (IDeg - IDet) -1.11 (95% CI -1.83; -0.40) mmol/l; p < 0.05. The present study confirmed the long-term safety and tolerability profile of IDeg in patients with T1DM. IDeg provided a lower risk of nocturnal confirmed hypoglycaemia than IDet.

Efficacy and safety of insulin degludec given as part of basal-bolus treatment with mealtime insulin aspart in type 1 diabetes: a 26-week randomized, open-label, treat-to-target non-inferiority trial.

AIMS: The efficacy and safety of insulin degludec (IDeg) was compared with insulin detemir (IDet), both administered once daily (OD) as basal treatment in participants with type 1 diabetes mellitus (T1DM). The primary outcome was non-inferiority of IDeg to IDet in glycated haemoglobin (HbA1c) reduction after 26 weeks. METHODS: This multinational, 26-week, controlled, open-label, parallel-group trial randomized adults with T1DM to IDeg or IDet as OD basal insulin treatment combined with mealtime bolus insulin aspart (IAsp). Participants with T1DM treated with any basal-bolus insulin regimen for ≥ 12 months prior to the trial, a mean HbA1c ≤ 10.0% (85.8 mmol/mol) and body mass index (BMI) ≤ 35.0 kg/m(2) at screening participated in the trial (IDeg: N = 302; IDet: N = 153). RESULTS: After 26 weeks, HbA1c decreased 0.73% (8.0 mmol/mol) (IDeg) and 0.65% (7.1 mmol/mol) (IDet) [estimated treatment difference (ETD) IDeg-IDet: -0.09% (-0.23; 0.05)95% CI (-10.0 mmol/mol [-2.6; 0.6]95% CI ); confirming non-inferiority]. Mean fasting plasma glucose improved in both groups, and was lower with IDeg than IDet [ETD IDeg-IDet: -1.66 mmol/l (-2.37; -0.95)95% CI , p < 0.0001]. The rate of confirmed hypoglycaemia was similar with IDeg and IDet [45.83 vs. 45.69 episodes per patient-year of exposure (PYE); estimated rate ratio (RR) IDeg/IDet: 0.98 (0.80; 1.20)95% CI , p = 0.86]. The rate of nocturnal confirmed hypoglycaemia was lower with IDeg than IDet [4.14 vs. 5.93 episodes per PYE; RR IDeg/IDet: 0.66 (0.49; 0.88)95% CI , p = 0.0049]. Adverse event profiles were similar between groups. CONCLUSION: IDeg administered OD in basal-bolus therapy effectively improved long-term glycaemic control in participants with T1DM with a lower risk of nocturnal confirmed hypoglycaemia than IDet.

Megaduodenum in a patient with acromegaly.

INTRODUCTION: Acromegaly is associated with enlargement of all organs including the gastro intestinal system. However, there are no previous reports of occurrence of megaduodenum in patients with acromegaly. DISCUSSION: We present the case of a 47 year old male who was diagnosed to have acromegaly 13 years ago and had undergone transsphenoidal surgery twice with incomplete removal of the pituitary macro-adenoma and received radiotherapy following the second surgery. Patient has been on replacement therapy for hypocortisolism, hypothyroidism and hypogonadism since 10 years. Post glucose growth hormone level continued to remain unsuppressed; however, patient never received any medical therapy for acromegaly. He was evaluated with esophago-gastro-duodenoscopy for recurrent abdominal pain and distension, which showed an elongated and tortuous megaduodenum. These findings were verified with a barium study which revealed dilated stomach, first and second part of duodenum with no evidence of a distal obstruction. CONCLUSIONS: We report this finding in view of the rare association.

Congenital adrenal hyperplasia - experience from a tertiary centre in South India.

Congenital adrenal hyperplasia is a group of autosomal recessive disorders caused by enzyme deficiency which leads to defects in biosynthesis of steroid precursors. Most common is 21 hydroxylase deficiency. Clinical spectrum varies from non-classical CAH to classic CAH, and it may be simple virilising form or salt-wastinfg type. 29 patients were included in our study from January 2012 to October 2012. 76% were females. Male babies typically presented with adrenal crisis between 3(rd) to 6(th) week of life. Around 20% of females were identified and appropriately treated only after late adolescence. Short stature was seen in 1/3(rd) of patients. 1/3(rd) of patients had suppressed 17 OHP levels suggestive of over-replacement therapy which may contribute to final reduction in adult height.

Bilateral gonadoblastomas with a left sided dysgerminoma in a true hermaphrodite (disorder of sexual differentiation) with 46, XY karyotype.

Ovotesticular DSD is not an uncommon disorder. The presence of Y chromosome confers a high risk of neoplastic transformation in dysgenetic gonads. The neoplastic development in these patients is associated with the presence of Y chromosome and intra abdominal location of the abnormal gonad. We report histogenetic details of a rare occurrence of bilateral gonadoblastomas and left sided dysgerminoma in a XY ovotestes DSD (disorder of sexual differentiation) in an 18 year old with a female phenotype.