Elevated Peripheral Brain-Derived Neurotrophic Factor Level Associated With Decreasing Insulin Secretion May Forecast Memory Dysfunction in Patients With Long-Term Type 2 Diabetes

BackgroundWith the progressive course of diabetes and the decline in islet function, the cognitive dysfunction of patients aggravated.ObjectiveWe aimed to investigate the roles of brain-derived neurotrophic factor (BDNF) and the Val66Met polymorphism in mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 169 Chinese patients with T2DM were involved and divided into long-term (diabetes duration >10 years) and short-term (diabetes duration ≤10 years) diabetes, and in each group, the patients were separated as MCI and the control. Demographic characteristics, clinical variables, and cognitive performances were assessed. The plasma BDNF level was measured via enzyme-linked immunosorbent assay. The Val66Met polymorphisms were analyzed.ResultsLong-term T2DM have lower 2 h postprandial C-peptide (p < 0.05). The BDNF level was slightly higher in patients with MCI than in the controls in each duration group without statistical significance. The relationship of BDNF to Montreal Cognitive Assessment was not proven either. However, in the long-term diabetes group, BDNF concentration remained as an independent factor of logical memory test (β = −0.27; p < 0.05), and they were negatively correlated (r = −0.267; p = 0.022); BDNF was also negatively correlated with fasting C-peptide (r = −0.260; p = 0.022), 2 h postprandial C-peptide (r = −0.251; p = 0.028), and homeostasis model assessment of insulin resistance (r = −0.312; p = 0.006). In genotypic groups, BDNF Val/Val performed better in logical memory test than Met/Met and Val/Met.ConclusionElevated peripheral BDNF level associated with declined islet function, when combined with its Val66Met polymorphism, may forecast memory dysfunction in patients with long-term T2DM.

Low-frequency electroacupuncture improves disordered hepatic energy metabolism in insulin-resistant Zucker diabetic fatty rats via the AMPK/mTORC1/p70S6K signaling pathway

Background and aim: Disordered hepatic energy metabolism is found in obese rats with insulin resistance (IR). There are insufficient experimental studies of electroacupuncture (EA) for IR and type 2 diabetes mellitus (T2DM). The aim of this study was to probe the effect of EA on disordered hepatic energy metabolism and the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/ribosomal protein S6 kinase, 70-kDa (p70S6K) signaling pathway. Methods: Zucker Diabetic Fatty (ZDF) rats were randomly divided into three groups: EA group receiving EA treatment; Pi group receiving pioglitazone gavage; and ZF group remaining untreated (n = 8 per group). Inbred non-insulin-resistant Zucker lean rats formed an (untreated) healthy control group (ZL, n = 8). Fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, C-reactive protein (CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were measured. Hematoxylin–eosin (H&E) staining was used to investigate the liver morphologically. The mitochondrial structure of hepatocytes was observed by transmission electron microscopy (TEM). Western blotting was adopted to determine protein expression of insulin receptor substrate 1 (IRS-1), mTOR, mTORC1, AMPK, tuberous sclerosis 2 (TSC2) and p70S6K, and their phosphorylation. RT-PCR was used to quantify IRS-1, mTOR, mTORC1, AMPK and p70S6K mRNA levels. Results: Compared with the ZF group, FPG, FINS, C-peptide, CRP and HOMA-IR levels were significantly reduced in the EA group ( p < 0.05, p < 0.01). Evaluation of histopathology showed improvement in liver appearances following EA. Phosphorylation levels of AMPK, mTOR and TSC2 decreased, and IRS-1 and p70S6K increased, in hepatocytes of the ZF group, while these negative effects appeared to be alleviated by EA. Conclusions: EA can effectively ameliorate IR and regulate energy metabolism in the ZDF rat model. AMPK/mTORC1/p70S6K and related molecules may represent a potential mechanism of action underlying these effects.

Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients

Background: glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. Methods: thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (ΔAUCGLUCA, ΔAUCGLU, ΔAUCINS) over the whole participants’ cohort. Results: in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p ≤ 0.006). In the whole cohort, ΔAUCGLUCA was weakly related to ΔAUCGLU (p ≤ 0.02), but not to ΔAUCINS, though basal insulin secretion emerged as possible covariate. Conclusions: glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.

Study of fasting & PP C- peptide & its correlation with HbA1c in T2 Diabetes mellitus in population of Uttarakhand

We aimed to provide correlation of Fasting & PP C-peptide with HbA1C in patients of T2 Diabetes Mellitus.: 50 patients admitted in IPD of Medicine department in Shri Mahant Indresh Hospital from April-August 2021. Serum samples taken for fasting & PP C-peptide and HbA1C for patients of T2 Diabetes Mellitus and run on VITROS 5600/7600 which is based on dry chemistry. : We took 50 patients who were T2DM then we did fasting C peptide & PP C-peptide and HbA1c. Out of 50, 15 were females &35 were males. Out of 50, 45 patients had raised HbA1C maximum around 8-10.Mean & SD for fasting C-Peptide for males was 1.346±1.070 & for females 2.442±2.57.Mean & SD for Post prandiol C-Peptide for males was 4.208±5.020 & for females 2.993±2.130.It was significant for fasting C- Peptide with P value 0.0371 and non significant for PP C peptide with p value 0.3731.: Insulin secretion estimated by measurement of Fasting C-Peptide was either normal or raised in newly diagnosed T2DM subjects in my study indicating predominant role of insulin resistence in the etiology. Further research can explore the exact contribution of insulin resistence and insulin secretory defects in this area.

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at one year following TPIAT in a cohort of children. <p>Research Design and Methods: This was a review of 43 pediatric patients followed after TPIAT for one year or longer. Primary outcome was insulin use at one year, categorized as: insulin independent, low (< 0.5 u/kg/day) or high insulin (≥ 0.5 u/kg/day) requirement. </p> <p>Results: At one year after TPIAT, 12/41 (29%) patients were insulin independent, 21/41 (51%) had low and 8/41 (20%) had high insulin requirement. Insulin independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; p=0.03). Patients with insulin independence had higher transplanted IEQ/kg (p=0.03) and lower body surface area (p=0.02), compared to those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (p=0.03). Higher peak C-peptide measured by stimulated mixed meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at one year (p=0.006 and 0.03, respectively). </p> <p>Conclusions: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ/kg transplanted and lower body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement. </p>

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at one year following TPIAT in a cohort of children. <p>Research Design and Methods: This was a review of 43 pediatric patients followed after TPIAT for one year or longer. Primary outcome was insulin use at one year, categorized as: insulin independent, low (< 0.5 u/kg/day) or high insulin (≥ 0.5 u/kg/day) requirement. </p> <p>Results: At one year after TPIAT, 12/41 (29%) patients were insulin independent, 21/41 (51%) had low and 8/41 (20%) had high insulin requirement. Insulin independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; p=0.03). Patients with insulin independence had higher transplanted IEQ/kg (p=0.03) and lower body surface area (p=0.02), compared to those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (p=0.03). Higher peak C-peptide measured by stimulated mixed meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at one year (p=0.006 and 0.03, respectively). </p> <p>Conclusions: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ/kg transplanted and lower body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement. </p>

Changes in Metabolic Regulation and the Microbiota Composition after Supplementation with Different Fatty Acids in db/db Mice

Introduction. The effects of fatty acids on health vary and depend on the type, amount, and route of consumption. EPA and DHA have a defined role in health, unlike coconut oil. Objective. The aim was to investigate the changes in metabolic regulation and the composition of the culture-dependent microbiota after supplementation with different fatty acids in db/db mice. Material and Methods. We were using 32 8-week-old db/db mice, supplemented for eight weeks with EPA/DHA derived from microalgae as well as coconut oil. The lipid, hormonal profiles, and composition of the culture-dependent microbiota and the phylogenetic analysis based on the 16S rRNA gene sequencing were determined for identification of the intestinal microbiota. Results. Enriched diet with EPA/DHA reduced TNF-α, C-peptide, insulin resistance, resistin, and the plasma atherogenic index, but increased TC, LDL-c, VLDL-c, and TG without changes in HDL-c. Coconut oil raised the HDL-c, GIP, and TNF-α, with TG, insulin resistance, adiponectin, and C-peptide reduced. Conclusion. The most abundant microbial populations were Firmicutes and the least Proteobacteria. EPA/DHA derived from microalgae contributes to improving the systemic inflammatory status, but depressed the diversity of the small intestine microbiota. Coconut oil only decreased the C-peptide, raising TNF-α, with an unfavorable hormonal and lipid profile.

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation

OBJECTIVE Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement (&lt;0.5 units/kg/day), or high insulin requirement (≥0.5 units/kg/day). RESULTS At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.