Glycemic Control In Type 2 Diabetes Research Articles

The effect of whole-body vibration on glucose and lipid profiles in type-2 diabetes: a systematic review and pairwise and network meta-analyses of randomized trials

Whole-body vibration (WBV), a training method based on the stimulation of muscle contraction by mechanical vibration generated in a vibrating platform, is claimed to be effective in diabetes management. This meta-analysis evaluated WBV effects against other exercises, placebo, or no intervention in type-2 diabetes. Medline, Scopus, and Web of Science databases were systematically searched through June 2023. Randomized controlled trials reported the effect of WBV on glucose (hemoglobin A1C and fasting blood glucose), and lipid profiles (total cholesterol, triglycerides, high, and low-density lipoprotein) were included. Two researchers independently extracted the characteristics of the studies, participants, WBV intervention and comparisons, and the outcomes from the included articles. The Physiotherapy Evidence Database (PEDro) scale assessed trial quality. In this review, all articles had no high risk of bias according to the PEDro scale, with studies achieving optimal, excellent, and good scores. Network meta-analysis revealed that WBV was effective for reducing hemoglobin A1C when compared with conventional (mean difference: − 1.58%, 95%CrI: − 2.51, − 0.47) and resistance exercise (mean difference: − 1.32%, 95%CrI: − 1.96, − 0.33). WBV had also a desirable but insignificant effect on hemoglobin A1C compared to stretching and balance exercises, placebo, and no intervention. The current pairwise meta-analysis did not show that WBV favors fasting blood glucose and lipids. WBV may have potential advantages for glycemic control in type-2 diabetes. However, uncertainties in the findings remain due to the limited number of studies and their heterogeneity.

The impact of major depressive disorder on glycaemic control in type 2 diabetes: a longitudinal cohort study using UK Biobank primary care records

BackgroundThis study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses.MethodsIn UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with disease duration included using restricted cubic splines. Four MDD exposures were considered: MDD diagnosis prior to T2D diagnosis (pre-T2D MDD), time between pre-T2D MDD diagnosis and T2D, new MDD diagnosis during follow-up (post-T2D MDD) and time since post-T2D MDD diagnosis. Models with and without covariate adjustment were considered.ResultsT2D diagnostic criteria were robustly associated with T2D polygenic scores. In 11,837 T2D cases (6.9 years median follow-up), pre-T2D MDD was associated with a 0.92 increase in HbA1c (95% CI: [0.00, 1.84]), but earlier pre-T2D MDD diagnosis correlated with lower HbA1c. These pre-T2D MDD effects became non-significant after covariate adjustment. Post-T2D MDD individuals demonstrated increasing HbA1c with years since MDD diagnosis (β=0.51\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta =0.51$$\\end{document}, 95% CI: [0.17, 0.86]). Retrospectively, across study follow-up, within-patient variability in HbA1c was 1.16 (95% CI: 1.13–1.19) times higher in post-T2D MDD individuals.ConclusionsThe timing of MDD diagnosis is important for understanding glycaemic control in T2D. Poorer control was observed in MDD diagnosed post-T2D, highlighting the importance of depression screening in T2D, and closer monitoring for individuals who develop MDD after T2D.

Imeglimin mitigates the accumulation of dysfunctional mitochondria to restore insulin secretion and suppress apoptosis of pancreatic β-cells from db/db mice

Mitochondrial dysfunction in pancreatic β-cells leads to impaired glucose-stimulated insulin secretion (GSIS) and type 2 diabetes (T2D), highlighting the importance of autophagic elimination of dysfunctional mitochondria (mitophagy) in mitochondrial quality control (mQC). Imeglimin, a new oral anti-diabetic drug that improves hyperglycemia and GSIS, may enhance mitochondrial activity. However, chronic imeglimin treatment’s effects on mQC in diabetic β-cells are unknown. Here, we compared imeglimin, structurally similar anti-diabetic drug metformin, and insulin for their effects on clearance of dysfunctional mitochondria through mitophagy in pancreatic β-cells from diabetic model db/db mice and mitophagy reporter (CMMR) mice. Pancreatic islets from db/db mice showed aberrant accumulation of dysfunctional mitochondria and excessive production of reactive oxygen species (ROS) along with markedly elevated mitophagy, suggesting that the generation of dysfunctional mitochondria overwhelmed the mitophagic capacity in db/db β-cells. Treatment with imeglimin or insulin, but not metformin, reduced ROS production and the numbers of dysfunctional mitochondria, and normalized mitophagic activity in db/db β-cells. Concomitantly, imeglimin and insulin, but not metformin, restored the secreted insulin level and reduced β-cell apoptosis in db/db mice. In conclusion, imeglimin mitigated accumulation of dysfunctional mitochondria through mitophagy in diabetic mice, and may contribute to preserving β-cell function and effective glycemic control in T2D.

Trends in clinical characteristics, medication use, and glycemic control in insulin-treated patients with type 1 and type 2 diabetes in Finland in 2012-2019: Nationwide real-world evidence study.

To describe the clinical characteristics and medication purchases of insulin-treated adults in Finland at index (January 1, 2012 or first insulin purchase) and December 31, 2019. Additionally, to describe basal insulin (BI) treatment patterns and associated changes in hemoglobin A1c (HbA1c) values. In this descriptive study using nationwide registries, we included adults with at least two reimbursed insulin purchases within 12 months of the first purchase between January 1, 2012 and December 31, 2019. We formed four study groups: type 1 diabetes (T1D) and type 2 diabetes (T2D)-diagnosed people who were further divided into prevalent or naïve users (start of insulin use before or after January 1, 2012). Insulin treatment patterns were estimated from medication purchase data and glycemic control from HbA1c results. Out of 145 020 people included, 34 359 had T1D and 110 661 T2D. By 2019, in parallel with the adaptation of new noninsulin medications, second-generation basal insulin (BI) analogues were adopted by 45.9% and 21.1% of prevalent T1D and T2D users. At index, HbA1c target (≤53 mmol/mol) was reached by 17% and 35% of T2D naïve and prevalent users, respectively, and by 17% of T1D prevalent users. At study end, the target was reached respectively by 41%, 34%, and 22% of insulin users. Insulin initiation improved and discontinuation worsened glycemic control in T2D, with lesser effects seen after treatment gaps or switches between BIs. Our study showed that glycemic control in insulin users has remained stable or improved between 2012 and 2019 despite aging population and in parallel with introduction of new treatment options, providing valuable insight into Finnish national diabetes care.

136-LB: The Implication of Glycemic Risk Index Varies with Different Levels of Glycosylation A1c (HbA1c) in Type 1 Diabetes

Objective: Type 1 diabetes (T1D) is characterized by significant fluctuations in blood glucose, necessitating comprehensive assessment of glycemic control. The Glucose Risk Index (GRI) is a new glucose assessment metric derived from continuous glucose monitoring (CGM) that can simultaneously indicate hyperglycemic and hypoglycemic risks. This study explored the implications of GRI for T1D with different HbA1c levels. Methods: We obtained 507 CGM and clinical data points from 281 patients with T1D, some of whom had follow-up data with intervals of over 3 months. The included patients aged 4-72 years with duration greater than 3 months and wore a CGM for at least 14 days. The hypoglycemic index and hyperglycemic index were calculated by time below range (TBR) <54 mg/dL + 0.8 × TBR <70-54 mg/dL and time above range (TAR) >250 mg/dL) + 0.5 × TAR >180-250 mg/dL, respectively. GRI is the sum of 3 times hypoglycemic index and 1.6 times hyperglycemic index. Relationships between GRI and HbA1c, each CGM metrics were explored and compared in patients with HbA1c <7% and ≥7%. Results: The mean GRI and HbA1c were 57.6 ± 20.6 and 7.3 ± 1.1%, respectively, and HbA1c of 7% approximately corresponded to GRI of 55. GRI was correlated with HbA1c (R = 0.536), hypoglycemic index (R = 0.466) and hyperglycemic index (R = 0.654), but the correlation between GRI and HbA1c disappeared in subgroup with HbA1c <7%. Compared with the HbA1c ≥7% group, GRI in the HbA1c <7% group had a stronger correlation with hypoglycemic index and a weaker correlation with hyperglycemic index. Further analysis showed the combination of dichotomous HbA1c (<7% or ≥7%) and GRI (<55 or ≥55) conferred best evaluation of glycemic control. Conclusions: The implication of GRI varies with different levels of HbA1c in T1D, with GRI mainly representing hypoglycemic risk when HbA1c <7%, and hyperglycemic risk when HbA1c ≥7%. A more comprehensive assessment of glycemic control in T1D should be the combination of dichotomous HbA1c and GRI. Disclosure B. He: None. Y. Xie: None. X. Li: None. Z. Zhou: None. Funding National Natural Science Foundation of China (81600649)

1486-P: Effects of the COVID-19 Booster Vaccine on Glycemia and Insulin Resistance in People with Type 1 Diabetes—A Prospective Pilot Study

Background: Inflammation is well-known to worsen glycemia in people with type 1 diabetes (T1D). COVID-19 vaccines are vital for protection against SARS-CoV-2 infection, but by necessity trigger an acute immune response. Case reports have described hyperglycemic crises shortly after a booster dose. However, effects of COVID-19 vaccines on glycemic control in T1D is poorly understood. Methods: This was a prospective cohort study of adults with T1D receiving a COVID-19 booster dose. At the baseline visit a blinded Dexcom G6 Pro CGM was placed, subjects received COVID-19 booster vaccine 3-4 days later, and returned 6 days post-vaccination to have the CGM removed. Primary outcome was change in mean daily glucose level from baseline. Secondary outcomes included total daily insulin dose (TDI), total daily insulin resistance (TDIR = mean glucose * TDI), and time in range (TIR = %glucose readings between 70-180mg/dL). Data were transformed as necessary to maintain normality. Results: We enrolled 20 adults with T1D; one subject was excluded for nonadherence with study procedures. Baseline characteristics included (mean±SD) age: 48.9±19.4y, sex: 68.4%F, BMI: 29.6±6.2kg/m2, A1c: 7.0±1.0%. 42% received a Moderna and 58% Pfizer-BioNTech booster. Mean glucose on Day#2 post-vaccination was significantly greater than baseline (165.1±27.4 vs 154.5±30.2 mg/dL, p=0.04), as was TDIR (7970±4113 vs 7036±3999; p=0.02). No other days had significant differences in glycemic metrics as compared to baseline. There were no differences in any outcome metrics between booster vaccine manufacturers. Conclusions: These results suggest that adults with T1D may experience transient glycemic elevations after receiving a COVID-19 booster. Clinicians may need to warn people with T1D to be more vigilant with glucose testing and insulin dosing temporarily after vaccination. Larger studies are warranted to corroborate these findings. Disclosure M.Zilbermint: Consultant; EMD Serono, Other Relationship; American Association of Clinical Endocrinologists. M.Motevalli: None. K.Batty: None. J.Venner-walcott: None. A.Edwards: None. T.Burley: None. K.Jackson: None. M.Akhtar: None. A.Demidowich: Research Support; Dexcom, Inc. Funding Dexcom, Inc. (IIS-2021-136)

Food insecurity, SNAP participation and glycemic control in low-income adults with predominantly type 2 diabetes: a cross-sectional analysis using NHANES 2007–2018 data

IntroductionDiabetes, characterized by elevated blood glucose levels, affects 13% of US adults, 95% of whom have type 2 diabetes (T2D). Social determinants of health (SDoH), such as food insecurity, are...

Efficacy and Safety of Ultra-rapid Lispro Insulin in Managing Type-1 and Type-2 Diabetes: A Systematic Review and Meta-Analysis.

Mechanistically, subcutaneous ultra-rapid lispro (URLi) is faster than lispro. Whether this translates into a better post-prandial glucose (PPG) and glycemic control in type-1 diabetes (T1DM) and type-2 diabetes (T2DM) is unclear. Hence, we undertook this meta-analysis. Databases were searched for randomized controlled trials (RCTs) involving patients with T1DM/T2DM receiving URLi in intervention-arm, and placebo/prandial insulin as control. The primary outcome was a change in PPG. Secondary outcomes were alterations in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), time in range (TIR), and adverse events. Data from six RCTs (3687 patients) were analyzed. Lispro was the control arm in all RCTs. T1DM patients receiving mealtime URLi had lower HbA1c [mean difference (MD) -0.07%; 95% confidence interval (CI): -0.12 to - 0.01; P = 0.02; I2 = 42%] and 1-h PPG [MD - 1.18 mmol/L; 95% CI: -1.91 to - 0.44; P = 0.002; I2 = 100%]. T1DM patients receiving post-meal URLi had comparable HbA1c [MD 0.07%; 95% CI: -0.01 to 0.15; P = 0.07; I2 = 55%] and 1-h PPG [MD 0.22 mmol/L; 95% CI: -0.80 to 1.24; P = 0.67; I2 = 100%). T1DM patients on pumps receiving URLi had comparable TIR [MD 1.70; 95% CI: -0.29 to 3.69; P = 0.09; I2 = 98%], lower time in blood glucose <3 mmol/L with increased infusion-set reactions. T2DM patients receiving mealtime URLi had lower 1-h PPG [MD - 0.66 mmol/L; 95% CI: -0.69 to - 0.63; P < 0.00001; I2 = 0%(LH), 2-h-PPG [MD - 0.96 mmol/L; 95% CI: -1.00 to - 0.92; P < 0.00001; I2 = 0%], higher FPG [MD 0.18 mmol/L; 95% CI: 0.11-0.24; P < 0.00001; I2 = 20%], and higher HbA1c [MD 0.07%; 95% CI: -0.06 to 0.08; P < 0.00001; I2 = 0%]. Pre-meal URLi is better than lispro with regard to PPG control. Post-meal URLi is as good as lispro for PPG control. Post-meal URLi is inferior to pre-meal URLi for PPG control.

Long-term efficacy of sensor-augmented pump therapy (Minimed 640G system) combined with a telemedicine follow-up in patients with type 1 diabetes: A real life study

ObjectiveEvaluate the efficacy of a new modality of insulin therapy associating both the sensor-augmented pump therapy with predictive low-glucose management (SAP-PLGM) and a telemedicine follow-up in patients with Type 1 diabetes (T1D) in a real-life setting. MethodsT1D adults under Minimed 640G system with a telemedicine follow-up for glucose management were included in a retrospective study. The primary endpoint was HbA1c while continuous glucose monitoring parameters (CGM) and treatment compliance were the secondary endpoints. These parameters were analyzed according to the therapeutic indication, HbA1c ≥ 8 % (GroupA) or severe hypoglycemic events (GroupB) and in patients switched to SAP-PLGM therapy. Results62patients were analyzed with a 28 ± 12 months of follow-up. In GroupA, HbA1c decreased from 8.3 ± 0.4 % to 7.7 ± 0.7 % (p < 0.05) and to 7.9 ± 0.3 % (p < 0.05) after 2 and 3 years, respectively. In patients switched to SAP-PLGM therapy, HbA1c decreased from 7.7 ± 0.7 % to 7.2 ± 0.8 % (p < 0.05) at 2 years. After 6 months, the time-below-range (<70 mg/dL) decreased from 2.1 % [0.6–4] to 1.1 % [0.3–2.6] (p < 0.05). Severe hypoglycemic events decreased from 1.62 to 0.5events/patient/year in GroupB (p < 0.05). At 3 years, treatment compliance was 92 % [70–97] in the total population. ConclusionsLong-term real-life treatment with the SAP-PLGM therapy combined with telemedicine was associated with improved glycemic control in T1D, along with high treatment compliance.

The Paradoxical Role of Circulating Ketone Bodies in Glycemic Control of Individuals with Type 2 Diabetes: High Risk, High Reward?

Introduction: Fasting plasma ketone bodies (KB) are elevated in individuals with type 2 diabetes (T2D) and could affect glycemic control and disease progression. Prolonged KB exposure may result in adaptive beneficial responses, counteracting glycemic dysregulation. In the current proof-of-concept study in adults with T2D, we hypothesized that fasting plasma KB are cross-sectionally associated with poorer glycemic control but prospectively with better glycemic control. Materials and Methods: Fasting plasma KB were measured via nuclear magnetic resonance spectroscopy in patients with T2D treated in primary care (Zodiac cohort; The Netherlands). We analyzed the associations between KB and HbA1c at baseline using linear regression analyses and HbA1c changes over time using linear mixed models. We adjusted for potential confounders, including risk factors for poor glycemic control. Individuals with T2D participating in the general population-based PREVEND study were used as a replication cohort. Results: We included 271 individuals with T2D with a total of 859 HbA1c measurements during a follow-up period of 3.0 (2.0–3.2) years. At baseline, the total amount of fasting plasma KB was independently and positively associated with HbA1c levels (regression coefficient in the fully adjusted analysis = 0.31; 95% CI 0.06–0.57, per doubling of KB; p = 0.02). In contrast, in the longitudinal analyses, fasting plasma KB were associated with a yearly HbA1c (%) decrease of −0.10 (95% CI −0.19 to −0.00 per doubling baseline KB; p = 0.05). Results were replicated in 387 individuals with T2D from a general population cohort with a total of 1115 glucose measurements during a follow-up period of 7.5 (7.2–8.0) years. A yearly decrease in fasting plasma glucose (mmol/L) of 0.09 was found per doubling of baseline KB. Conclusions: This study is the first to suggest a paradoxical role of circulating KB on glycemic control in T2D: elevated KB are associated with cross-sectionally poorer glycemic control but longitudinally with better long-term glycemic control.

Sleep optimization to improve glycemic control in adults with type 1 diabetes: study protocol for a randomized controlled parallel intervention trial

BackgroundDespite improvements in treatment regimens and technology, less than 20% of adults with type 1 diabetes (T1D) achieve glycemic targets. Sleep is increasingly recognized as a potentially modifiable target for improving glycemic control. Diabetes distress, poor self-management behaviors, and reduced quality of life have also been linked to sleep variability and insufficient sleep duration. A significant gap of knowledge exists regarding interventions to improve sleep and the effects of sleep optimization on glycemic control in T1D. The purpose of this study is to determine the efficacy of a T1D-specific sleep optimization intervention (Sleep-Opt) on the primary outcomes of sleep variability, sleep duration, and glycemic control (A1C); other glycemic parameters (glycemic variability, time-in-range [TIR]); diabetes distress; self-management behaviors; quality of life; and other patient-reported outcomes in adults with T1D and habitual increased sleep variability or short sleep duration.MethodsA randomized controlled parallel-arm study will be employed in 120 adults (aged 18 to 65 years) with T1D. Participants will be screened for habitual sleep variability (> 1 h/week) or insufficient sleep duration (< 6.5 h per night). Eligible subjects will be randomized to the Sleep-Opt intervention group or healthy living attention control group for 12 weeks. A 1-week run-in period is planned, with baseline measures of sleep by actigraphy (sleep variability and duration), glycemia (A1C and related glycemic measures: glycemic variability and TIR using continuous glucose monitoring), and other secondary outcomes: diabetes distress, self-management behaviors, quality of life, and additional patient-reported outcomes. Sleep-Opt is a technology-assisted behavioral sleep intervention that we recently developed that leverages the rapidly increasing public interest in sleep tracking. Our behavioral intervention employs four elements: a wearable sleep tracker, didactic content, an interactive smartphone application, and brief telephone counseling. The attention control group will participate in a healthy living information program. Baseline measures will be repeated at midpoint, program completion, and post-program (weeks 6, 12, and 24, respectively) to determine differences between the two groups and sustainability of the intervention.DiscussionA better understanding of strategies to improve sleep in persons with T1D has the potential to be an important component of diabetes.Trial registrationClinical Trial Registration: NCT04506151.

HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control

BackgroundReduced cholesterol efflux capacity (CEC) of HDLs is likely to increase cardiovascular risk in type 1 diabetes (T1D). We aimed to assess whether improvement of glycemic control in T1D patients is associated with changes in CEC in relation with changes in carbamylation of HDLs.MethodsIn this open-label trial, 27 uncontrolled T1D patients were given a three-month standard medical intervention to improve glycemic control. HDL fraction was isolated from plasma, and CEC was measured on THP-1 macrophages. Carbamylation of HDLs was evaluated by an immunoassay. Control HDLs from healthy subjects were carbamylated in vitro with potassium cyanate.ResultsHbA1c decreased from 11.4% [10.2–12.9] (median [1st–3rd quartiles]) at baseline to 8.1% [6.6–9.0] after the three-month intervention (P < 0.00001). The CEC of HDLs increased after intervention in 19 (70%) patients (P = 0.038). At the same time, the carbamylation of HDLs decreased in 22 (82%) patients after intervention (P = 0.014). The increase in CEC significantly correlated with the decrease in carbamylated HDLs (r = −0.411, P = 0.034), even after adjustment for the change in HbA1c (β = −0.527, P = 0.003). In vitro carbamylation of control HDLs decreased CEC by 13% (P = 0.041) and 23% (P = 0.021) using 1 and 10 mmol/L of potassium cyanate, respectively.ConclusionsThe improvement of CEC in relation to a decrease in the carbamylation of HDLs may likely contribute to the beneficial cardiovascular effect of glycemic control in T1D patients.Trial registration: NCT02816099 ClinicalTrials.gov.

Effects of resistance training on the glycemic control of people with type 1 diabetes: a systematic review and meta-analysis.

Resistance training has shown the potential to contribute to better glycemic control in people with Type 1 Diabetes (T1D), however, there are contradictory results in this regard and a need to clarify the effects of isolated resistance training on glycemic control in T1D. The aim was to verify the effects of resistance training on the glycemic control of people with T1D. Original articles were selected, randomized and non-randomized clinical trials that aimed to verify chronic responses, through the concentrations of glycated hemoglobin (HbA1c), to a structured program of resistance exercise in the glycemia of patients with T1D. The following databases were searched; MEDLINE, PubMed, Web of Science, Scopus, ScienceDirect, LILACS, and SciELO. Five studies were included in the review. A reduction in HbA1c was observed (SMD = -0.568 ± 0.165 [95% CI = -0.891 to -0.246]; p = 0.001; I2 = 82%) in patients undergoing resistance training, when compared to the control group (SMD = 1.006 ± 0.181 [95% CI = 0.653 to 1.360]; p <0.001). Two studies, with children and adolescents and longer interventions, demonstrated a significant reduction in HbA1c, increased strength, and an improved lipid profile. Resistance training was efficient for assisting in glycemic control in people with T1D and should be incorporated in treatment plans.

Associations of Dietary Antioxidants with Glycated Hemoglobin and Insulin Sensitivity in Adults with and without Type 1 Diabetes.

Type 1 diabetes (T1D) has been associated with increased risks of atherosclerotic cardiovascular disease, and poor glycemic control and oxidative stress play a major role in its pathology. There is a lack of data on the role of dietary antioxidant micronutrients, including vitamins and trace elements, in glycemic control in T1D. The aim of this study is to examine associations of dietary intakes of micronutrients with glycemic status. We report data from a cross-sectional analysis from the coronary artery calcification in type 1 diabetes (CACTI) study (n = 1257; T1D: n = 568; nondiabetic controls: n = 689) collected between the years 2000 and 2002. Participants completed a validated food frequency questionnaire, a physical examination, and biochemical analyses. Linear regression was used to examine the associations of dietary antioxidant micronutrients with HbA1c and estimated insulin sensitivity (eIS) in models adjusted for relevant covariates and stratified by diabetes status. In adults with T1D, we observed higher dietary manganese intake associated with higher eIS in the model adjusted for age, sex, diabetes duration, and total calories. In nondiabetic controls, higher intake of manganese associated with lower HbA1c and higher eIS values that persisted in models adjusted for all relevant covariates. On the other hand, dietary copper revealed a positive association with HbA1c in models adjusted for all covariates, except BMI and plasma lipids. No associations were noted for vitamins C and E and dietary carotenoids in either group. These findings reveal dietary antioxidant micronutrients, especially trace elements such as copper and manganese deserve special attention in glycemic control in adults with T1D as well as in nondiabetic controls.This trial is register with NCT00005754.

Glycemic control, depression, diabetes distress among adolescents with type 2 diabetes: effects of sex, race, insurance, and obesity.

To determine (1) differences in depression and distress scores between adolescents with type 1 (T1D) and type 2 diabetes (T2D), (2) how socioeconomic factors, obesity, race, and treatment regimen affect depression and diabetes distress in adolescent T2D, (3) the relationships between depression and diabetes distress scores in adolescents with T2D, and (4) how depression and diabetes distress scores relate to current and future glycemic control in adolescents with T2D. Diabetes distress is a negative emotional reaction to diabetes complications, self-management demands, unresponsive providers, poor interpersonal relationships, and to diabetes itself. It is frequently mistaken for depression and the two are interrelated. Increases in both predict poor glycemic control in adolescents with T1D. Depression (PHQ-9) and diabetes distress (PAID-T) scores from self-administered tests were studied in 364 patients with diabetes between the ages of 13-17. Kruskal-Wallis test was used to assess differences between types of diabetes, sexes, races, and insurance status. Spearman correlations, and robust rank order multivariable regression analysis were used to assess relationships. Medical records were reviewed for follow-up hemoglobin A1c (HbA1c) levels over 3years. HbA1c was significantly lower in females with T2D than with T1D (p = 0.019) but not in males. It, also, did not differ between females and males with T2D. Median PHQ-9 score in females with T2D was significantly greater than in females with T1D (p = 0.007) but did not differ between females and males with T2D. PHQ-9 scores did not differ between males with T2D and T1D. PAID-T scores, however, were higher in males with T2D than in males with T1D but did not differ between females. PHQ-9 scores and PAID-T scores were significantly related in T2D (rs = 0.65, p < 0.001). Neither was related to HbA1c in T2D. As in adolescents with T1D, depression and diabetes distress screening scores are closely related in adolescent T2D. However, unlike T1D, they are not related to glycemic control in T2D. Depression and diabetes distress may be more closely related to weight and lifestyle concerns.

Neuropeptide Y1 receptor antagonism protects β-cells and improves glycemic control in type 2 diabetes

ObjectivesLoss of functional β-cell mass is a key factor contributing to poor glycemic control in advanced type 2 diabetes (T2D). We have previously reported that the inhibition of the neuropeptide Y1 receptor improves the islet transplantation outcome in type 1 diabetes (T1D). The aim of this study was to identify the pathophysiological role of the neuropeptide Y (NPY) system in human T2D and further evaluate the therapeutic potential of using the Y1 receptor antagonist BIBO3304 to improve β-cell function and survival in T2D. MethodsThe gene expression of the NPY system in human islets from nondiabetic subjects and subjects with T2D was determined and correlated with the stimulation index. The glucose-lowering and β-cell-protective effects of BIBO3304, a selective orally bioavailable Y1 receptor antagonist, in high-fat diet (HFD)/multiple low-dose streptozotocin (STZ)-induced and genetically obese (db/db) T2D mouse models were assessed. ResultsIn this study, we identified a more than 2-fold increase in NPY1R and its ligand, NPY mRNA expression in human islets from subjects with T2D, which was significantly associated with reduced insulin secretion. Consistently, the pharmacological inhibition of Y1 receptors by BIBO3304 significantly protected β cells from dysfunction and death under multiple diabetogenic conditions in islets. In a preclinical study, we demonstrated that the inhibition of Y1 receptors by BIBO3304 led to reduced adiposity and enhanced insulin action in the skeletal muscle. Importantly, the Y1 receptor antagonist BIBO3304 treatment also improved β-cell function and preserved functional β-cell mass, thereby resulting in better glycemic control in both HFD/multiple low-dose STZ-induced and db/db T2D mice. ConclusionsOur results revealed a novel causal link between increased islet NPY-Y1 receptor gene expression and β-cell dysfunction and failure in human T2D, contributing to the understanding of the pathophysiology of T2D. Furthermore, our results demonstrate that the inhibition of the Y1 receptor by BIBO3304 represents a potential β-cell-protective therapy for improving functional β-cell mass and glycemic control in T2D.

Effects of BTI320 on Glycemic Control in Patients with Type 2 Diabetes

Background/Purpose: Treatment of Type 2 diabetes (T2D) remains an unmet need, particularly a medication with low toxicity. BTI320 (SugarDown®) is fractionated galactomannan with inhibitory activity on carbohydratehydrolyzing enzymes. The primary objective of this study was to investigate the efficacy and safety of BTI320 on glycemic control in T2D. Subjects/Methods: This was a double-blind, placebo-controlled, multi-center study in 60 T2D adults. Subjects ingested 4 g BTI320 or placebo 10 minutes before meals 3 times daily for 12 weeks. The primary endpoint was the change from Baseline to Week 12 in 2-hr post-prandial glucose (PPG) AUC between groups. Results/Conclusion: A consistent trend was observed in favor of BTI320 vs. placebo in change from Baseline at Week 12 in 2-hr PPG AUC (-795.00 vs. -228.75 mg/dL*min), HbA1c (-0.7% vs. +1.1%), lipids, weight/BMI, and blood pressure. At Week 12, BTI320 had more subjects with stable glucose levels (84.6% vs. 79.2%). According to CGM, the BTI320 group had more subjects with stable glucose levels (84.6 vs. 79.2%) and BTI320 subjects experienced relative hypoglycemia for shorter duration than placebo consistently across all visits. No differences were observed in AE profiles between groups. BTI320 was proven to be efficacious and safe in T2D. This study is registered at ClinicalTrials.gov (NCT03655535).

The impact of treatment with antidepressants on HBA1c- and LDL levels in type 2 diabetes: A real-world within-subject study

IntroductionWith regard to glycemic control in type 2 diabetes (T2D), treatment with antidepressant drugs is a double-edged sword. Real-world, population-based data on the impact of antidepressant treatment on glycemic control in T2D is absent from the literature.ObjectivesTo estimate the impact of treatment initiation or termination with an antidepressant on HbA1c levels in individuals with T2D.MethodsPopulation-based, within-subject, study design examining HbA1c levels in the 16 months leading up to - and the 16 months following - antidepressant treatment initiation or termination, respectively. All individuals with newly developed T2D between 1 January 2000 and 31 October 2016 were identified. Study population 1 consisted of individuals that initiated antidepressant treatment after incident T2D and age- and sex matched individuals with T2D and without antidepressant treatment. Study population 2 consisted of individuals with prevalent antidepressant use at the time of incident T2D, who terminated antidepressant treatment during follow-up, and age- and sex matched individuals with T2D and without antidepressant treatment.ResultsAntidepressant treatment initiation was associated with a decrease in HbA1c levels (7.05% to 6.89%). The age- and sex matched individuals did not have a change in mean HbA1c levels after the matched date. Antidepressant treatment termination was associated with a decrease in HbA1c levels (7.05% to 6.73%). Age- and sex matched individuals did not see a change in HbA1c levels after the matched date.ConclusionsThese findings suggest that antidepressant treatment initiation is not associated with adverse effects with regard to glycemic control in T2D. Rather, the data are indicative of a beneficial effect.Conflict of interestAarhus University funded the study. CR was supported by the Danish Diabetes Academy, funded by the Novo Nordisk Foundation, grant number NNF17SA0031406. The funders had no role in the study design, data analysis, interpretation of data, or writing of the

Associations of Dietary Patterns and Nutrients with Glycated Hemoglobin in Participants with and without Type 1 Diabetes.

Background: Diet has been associated with poor glycemic control in diabetes. Few studies have examined this association in people with type 1 diabetes (T1D), who are at a higher risk for cardiovascular disease than people without diabetes. Methods: We report data from cross-sectional and longitudinal analyses from a coronary artery calcification in type 1 diabetes (CACTI) study (n = 1257; T1D: n = 568; non-diabetic controls: n = 689) collected between the years 2000 and 2002. Participants completed a validated food frequency questionnaire, a physical examination, and biochemical analyses. Dietary patterns based on variations in food group intake were created with principal components analysis. Linear regression was used to examine the associations of dietary patterns, macronutrients, and food groups with HbA1c in a model adjusted for relevant covariates and stratified by diabetes status. Results: Three dietary patterns were identified: “fruits, veggies, meats, cereal”, “baked desserts” and “convenience foods and alcohol” patterns. At baseline, a higher intake of the “baked dessert” pattern was significantly associated with higher HbA1c in T1D at baseline as well at year 6 of the study when adjusted for age, sex, BMI, total calories, and diabetes duration. No such associations were observed in the case of non-diabetic controls. Dietary saturated fats and animal fats were also positively associated with HbA1c in adults with T1D at baseline and/or at year 6. Conclusions: The habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts, may increase risks of poor glycemic control in T1D.

Insulin resistance-associated genetic variants in type 1 diabetes.

To examine candidate insulin resistance single nucleotide polymorphisms (SNPs) for associations with glycemic control, insulin resistance, BMI, and complications in an observational type 1 diabetes (T1D) cohort: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study. In 422 European-ancestry participants, we assessed associations using additive models between 15 candidate SNPs and 25-year mortality, cardiovascular disease, microalbuminuria, overt nephropathy and proliferative retinopathy, and 25-year mean HbA1c, estimated glucose disposal rate (eGDR, inverse measure of insulin resistance), and BMI. The A allele of rs12970134 was associated with higher mean HbA1c (β = +0.34 ± 0.09, p = 0.00009) and nominally associated with worse eGDR (p = 0.02). Further analyses suggest the HbA1c association may be modified by diabetes therapy regimen: rs12970134 AA genotype was associated with higher HbA1c under non-intensive therapy conditions (<3 insulin injections/day or monitoring blood glucose<3 times/day [p = 0.004]), but not under intensive therapy (≥3 injections/day or insulin pump and monitoring glucose≥3 times/day [p = 0.71]). There were no significant associations between any SNPs and BMI or complications. rs12970134, near MC4R, is strongly associated with HbA1c in this cohort. Further exploration of this genomic region is warranted, as it may hold promise for discovering new therapeutic targets to improve glycemic control in T1D.