Lower HbA1c Research Articles

Lignan Intake and Type 2 Diabetes Incidence Among US Men and Women

Lignans are phytoestrogens abundant in Western diets and may be associated with type 2 diabetes (T2D) risk. To prospectively investigate associations between lignan intake and T2D incidence. Population-based cohort study of US men and women enrolled in the Nurses' Health Study (NHS, 1984-2018), NHSII (1991-2019), and Health Professionals Follow-Up Study (HPFS, 1986-2020), as well as 496 participants from the Men's Lifestyle Validation Study (MLVS). Participants were free of T2D, cardiovascular disease, and cancer at baseline. Data were analyzed from November 2022 to July 2023. Total and individual lignans were assessed using a validated food frequency questionnaire, which was updated every 2 to 4 years. In the MLVS, lignan intake was measured using 2 sets of 7-day diet records (7DDRs). Incident T2D cases were confirmed using American Diabetes Association diagnostic criteria. Cox proportional hazards models were used to assess multivariable-adjusted associations. The current study included 201 111 participants (mean [SD] age, 44.7 [10.1] years; 161 169 female participants [80.2%]; 2614 African American participants [1.3%], 1609 Asian participants [0.8%], 2414 Hispanic and other race or ethnicity participants [1.2%], and 194 474 White participants [96.7%]) from the HPFS, NHS, and NHSII studies. The median (IQR) total lignan intake of the highest quintile ranged from 355.1 (330.2-396.9) μg/d in NHS to 459.9 (422.2-519.5) μg/d in HPFS at the median follow-up time. Over 5 068 689 person-years, 20 291 incident cases of T2D were identified. Higher lignan intake was inversely associated with T2D incidence, except for lariciresinol. The multivariable-adjusted pooled hazard ratios (HRs) for the highest vs lowest quintiles were 0.87 (95% CI, 0.83-0.91) for total lignans, 0.72 (95% CI, 0.69-0.76) for secoisolariciresinol, 0.92 (95% CI, 0.87-0.96) for pinoresinol, 0.93 (95% CI, 0.89-0.98) for matairesinol, and 0.99 (95% CI, 0.94-1.04) for lariciresinol. Secoisolariciresinol intake exhibited a significant inverse association with T2D risk among individuals with obesity (HR, 0.75 for body mass index [BMI] ≥30; 95% CI, 0.71-0.79 vs HR, 0.82 for BMI <25; 95% CI, 0.81-0.83; P < .001 for interaction) and premenopausal women (HR, 0.67 for premenopausal women; 95% CI, 0.65-0.69 vs HR, 0.82 for the past use of hormones; 95% CI, 0.76-0.88; P = .003 for interaction). Dietary lignan assessed with 7DDRs was associated with lower HbA1c levels (percentage change range from -0.92% to 1.50%), as well as lower C-reactive protein levels and better lipid profiles. This cohort study found that long-term lignan consumption was associated with a lower T2D risk, particularly among individuals with obesity and premenopausal women.

Ductal Intervention in Chronic Pancreatitis: Impact on Glycemic Control and Endocrine Insufficiency Management.

Background and aim Pancreatic endotherapy has been established as a viable and effective modality for the management of pain in chronic pancreatitis (CP). However, its impact on endocrine insufficiency has been rarely reported. In this retrospective study, we aimed to assess the impact of endotherapy on glycemic status and the management of diabetes in these patients. Methods A retrospective review of a prospectively maintained database of patients with CP with pain presenting to the King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India, from December 2021 to May 2023 was done. Detailed clinical, laboratory, imaging, and treatment data were recorded. Endocrine dysfunction was defined as glycosylated hemoglobin (Hba1C) ≥6.5 g/dl. The status of endocrine function (Hba1C values) before and after endotherapy, as well as the requirement of oral hypoglycemic agent (OHA) and/or insulin, was recorded. Results One hundred forty-one patients underwent endoscopic retrograde cholangiopancreatography for the management of pain (mean age: 35 years, 74.5% males). Prior to endotherapy, pathological endocrine dysfunction was seen in 60 patients (42.5%). The mean HbA1c value was 8.46 g/dl (4.5-16.1g/dl). OHAs alone were used in 13/60 (21.6%), and 34/60 (56.6%) required insulin. A combination of OHA and insulin was required in 13/60 (21.6%) of patients. Post-endotherapy, none of the patients were on a combination of OHAs and insulin; 5/13 (38.4%) patients were on OHAs alone, while 8/13 (61.5%) patients were shifted to insulin. Out of the total 47 patients who required insulin, insulin could be stopped in 15/47 (31.9%) of patients. Patients who demonstrated improvement in endocrine dysfunction had significantly lower HbA1c values (6.38 vs. 8.07 g/dl, p < 0.001), a higher proportion of patients with idiopathic pancreatitis (73.3% vs. 22.2%, p = 0.004), and a lower proportion of patients with concomitant exocrine insufficiency (13.3% vs. 53.3%, p = 0.007). Conclusions One-third of the patients had improvements in endocrine dysfunction. Early ductal intervention in a selected subset of patients with CP may have the potential to improve glycemic status.

Glycated Hemoglobin A1c Time in Range and Dementia in Older Adults With Diabetes

Individuals with diabetes commonly experience Alzheimer disease and related dementias (ADRD). Factors such as hypoglycemia, hyperglycemia, and glycemic variability have been associated with increased risk of ADRD. Traditional glycemic measures, such as mean glycated hemoglobin A1c (HbA1c), may not identify the dynamic and complex pathophysiologic factors in the association between diabetes and ADRD. The HbA1c time in range (TIR) is a previously developed measure of glycemic control that expresses HbA1c stability over time within specific ranges. This measure may inform the current understanding of the association between glucose levels over time and ADRD incidence. To examine the association between HbA1c TIR and incidence of ADRD in older veterans with diabetes. The study sample for this cohort study was obtained from administrative and health care utilization data from the Veterans Health Administration and Medicare from January 1, 2004, to December 31, 2018. Veterans 65 years or older with diabetes were assessed. Participants were required to have at least 4 HbA1c tests during the 3-year baseline period, which could start between January 1, 2005, and December 31, 2014. Data analysis was conducted between July and December 2023. Hemoglobin A1c TIR was calculated as the percentage of days during baseline in which HbA1c was in individualized target ranges based on clinical characteristics and life expectancy, with higher HbA1c TIR viewed as more favorable. The association between HbA1c TIR and ADRD incidence was estimated. Additional models considered ADRD incidence in participants who were above or below HbA1c target ranges most of the time. The study included 374 021 veterans with diabetes (mean [SD] age, 73.2 [5.8] years; 369 059 [99%] male). During follow-up of up to 10 years, 41 424 (11%) developed ADRD. Adjusted Cox proportional hazards regression models showed that lower HbA1c TIR was associated with increased risk of incident ADRD (HbA1c TIR of 0 to <20% compared with ≥80%: hazard ratio, 1.19; 95% CI, 1.16-1.23). Furthermore, the direction of out-of-range HbA1c levels was associated with incident ADRD. Having greater time below range (≥60%, compared with ≥60% TIR) was associated with significantly increased risk (hazard ratio, 1.23; 95% CI, 1.19-1.27). Findings remained significant after excluding individuals with baseline use of medications associated with hypoglycemia risk (ie, insulin and sulfonylureas) or with hypoglycemia events. In this study of older adults with diabetes, increased HbA1c stability within patient-specific target ranges was associated with a lower risk of ADRD. Lower HbA1c TIR may identify patients at increased risk of ADRD.

The moderating role of diabetes distress on the effect of a randomized eHealth intervention on glycemic control in Black adolescents with type 1 diabetes.

Due to systemic inequities, Black adolescents with type 1 diabetes are more likely to have suboptimal glycemic control and high rates of diabetes distress, but tailored interventions for this population are lacking. In primary outcomes of a randomized clinical trial, a family-based eHealth intervention improved glycemic control in Black adolescents with type 1 diabetes and elevated depressive symptoms. The present study is a secondary analysis of these clinical trial data examining the moderating effect of diabetes distress on the efficacy of the intervention. Using secondary data from a multicenter randomized clinical trial (Clinicaltrials.gov [NCT03168867]), caregiver-adolescent dyads were randomly assigned to either up to three sessions of an eHealth parenting intervention (n = 75) or a standard medical care control group (n = 74). Black adolescents (10 years, 0 months to 14 years, 11 months old) with type 1 diabetes and a caregiver willing to participate were eligible. Adolescents reported their diabetes distress at baseline, and hemoglobin A1c (HbA1c) data were collected at baseline, 6-, 13-, and 18-month follow-up. No between-group contrasts emerged in a linear mixed-effects regression (p's > .09). Within-group contrasts emerged such that adolescents assigned to the intervention who reported high diabetes distress had lower HbA1c at the 18-month follow-up relative to baseline (p = .004); the 18-month decrease in HbA1c was -1.03%. Black adolescents with type 1 diabetes and high levels of diabetes distress showed significant decreases in HbA1c following a family-based eHealth intervention, suggesting diabetes distress may be a key moderator of intervention efficacy within this population.

Diabetes‐related distress in people with type 2 diabetes: experience from a community diabetes clinic

AbstractBackground: Diabetes distress is the term used to describe the diabetes‐specific emotional distress resulting from the challenges of managing this demanding chronic condition.Aims: This study aimed to determine the prevalence of diabetes distress and its subtypes in adults with type 2 diabetes who attended our community‐based clinics and to investigate the relationship between diabetes distress scores and demographic factors and diabetes variables (HbA1c and treatment regimen).Methods: Patients were referred to our specialist diabetes team by primary care teams. Clinical details, including current treatment regimen and recent HbA1c result, were recorded. Patients then completed the Diabetes Distress Scale (DDS) 17 questionnaire. Data from all 82 patients who attended our clinic from May 2022 to November 2022 were analysed.Results: A high level of diabetes distress (mean score of ≥3) was found in 17 patients (20.7%), and a moderate level of diabetes distress was found in 22 patients (26.8%). Patients with an HbA1c of &gt;90mmol/mol had significantly higher mean regimen‐related distress than those with an HbA1c of &lt;60mmol/mol (2.58±1.18 vs 1.86±0.8, respectively; p=0.03). In addition, patients with higher HbA1c had higher diabetes‐related emotional distress than those with lower HbA1c. However, this result did not demonstrate statistical significance. Conversely, patients with optimal HbA1c levels had significantly lower mean interpersonal distress scores than the rest of the cohort (1.13±0.99 vs 1.80±0.99, respectively; p=0.01).Conclusions: Diabetes distress is common among patients attending community‐based diabetes services. Further research is needed to determine the most effective strategies for reducing diabetes distress and improving clinical outcomes.

Potential of Fasting C-peptide to Glucose Ratio and Triglyceride Glucose Index as Markers for β-Cell Dysfunction and Insulin Resistance in Patients With Type 2 Diabetes on Insulin Therapy.

Pathogenesis of type 2 diabetes mellitus (T2DM) is combined from initial insulin resistance (IR) and subsequent β-cell dysfunction. Insulin therapy can replace β-cell function in advanced stages. However excessive insulin therapy increases IR and may expose the patients to risk of cardiovascular disease. We aim to assess β-cell function and IR in patients with type 2 diabetes on insulin therapy by fasting C-peptide to glucose ratio (FCPGR), and triglyceride glucose (TyG) index respectively to support treatment plans. A cross-sectional study was conducted at the Galiawa Diabetes and Endocrinology Teaching Center in Erbil City, Iraq,from June 2023 to January 2024. A convenient sample of 100 patients with T2DM on insulin-based therapy were included after obtaining informed written consent and excluding conditions such as acute illness,uncertain type of diabetes, etc. Each patient was evaluated for anthropometric parameters and current treatment details. Biochemical tests were then carried out to calculate metabolic syndrome (MetS) index score, FCPGR, and TyG index. Finally, patients were divided into four subgroups according to their FCPGR and TyG index and the data were analyzed statistically. The data showed those patients with sufficient β-cell function were 60(60%), and patients withhigh TyG index were 95 (95%). There was a significant negative correlation betweenFCPGR and hemoglobin A1c (HbA1c) (p-value=0.001), while there was a positive correlation between TyG index and HbA1C (p-value=0.001). None of these markers were correlated with BMI (p-value=0.297, and 0.976), duration of T2DM (p-value=0.258, and 0.458), and dose of insulin therapy (p-value=0.901, and 0.477). Patients with sufficient β-cell function and high TyG index had the lowest HbA1C. The study provides valuable insights into the utility of FCPGR and TyG index as biomarkers for β-cell function and insulin resistance in T2DM patients on insulin therapy. The significant correlation with HbA1C underscores their potential in clinical practice. However, the lack of correlation with BMI, disease duration, and insulin dose suggests that further investigation is needed to fully understand these biomarkers' implications across diverse patient profiles.

Severe Hypertriglyceridemia in Patients with Type 2 Diabetes Mellitus Participating in the AMD Annals Initiative.

Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the most severe forms. Aim of the Study: We investigated the prevalence and clinical characteristics associated with severe hypertriglyceridemia in a range indicative of FCS, in a large population of subjects with T2D. Methods: Within the large population of the AMD Annals Initiative, patients with T2D with a lipid profile suggestive of FCS [triglycerides >880 mg/dL and/or high-density lipoprotein (HDL)-cholesterol <22 mg/dL or non-HDL-cholesterol ≤70 mg/dL] and their clinical features have been identified. Results: Overall, 8592 patients had triglyceride values >880 mg/dL in a single examination, 613 in two examinations, and 34 in three or more measurements. Patients with high triglyceride levels were mostly male (80%), with a relatively young age (54 years), short duration of diabetes (6.3 years), and elevated hemoglobin A1c (HbA1c) levels (9.4%). By stratifying this group of patients according to the severity of hypertriglyceridemia, more severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL) was associated with an even younger age (52 vs. 54 years), even higher mean HbA1c values (10.0% vs. 9.4%), and significantly higher HDL-cholesterol levels (37.9 vs. 32.4 mg/dL; P < 0.0001). Patients with persistently elevated triglyceride levels (n = 34), on three measurements, had a younger age; lower body mass index, HbA1c, and HDL-cholesterol levels; more frequent use of fibrates and insulin; and a higher prevalence of major cardiovascular events. Conclusions: Severe hypertriglyceridemia is a frequent condition in outpatients with T2D participating in the AMD Annals Initiative, and it is associated with male sex, young age, short disease duration, and a worse glycemic profile. Among patients with persistent severe hypertriglyceridemia, hidden FCS may be present.

Mortality and cardiovascular events in diabetes mellitus patients at dialysis initiation treated with glucagon-like peptide-1 receptor agonists

BackgroundGlucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored.PurposeThis study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement.MethodsA cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE).ResultsAmong 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m2. GLP-1RAs’ new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE.ConclusionGiven to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis.

Differences Between Glycated Hemoglobin and Glucose Management Indicator in Real-Time and Intermittent Scanning Continuous Glucose Monitoring in Adults With Type 1 Diabetes.

This study demonstrates the difference between glucose management indicator (GMI) and glycated hemoglobin (HbA1c) according to sensor mean glucose and HbA1c status using 2 continuous glucose monitoring (CGM) sensors in people with type 1 diabetes. A total of 275 subjects (117 Dexcom G6 [G6] and 158 FreeStyle Libre 1 [FL]) with type 1 diabetes was included. The G6 and FL sensors were used, respectively, over 90 days to analyze 682 and 515 glycemic profiles that coincide with HbA1c. The mean HbA1c was 6.6% in Dexcom G6 and 7.2% in FL profiles. In G6 profiles, GMI was significantly higher than HbA1c irrespective of mean glucose (all P < .001, mean difference: 0.58% ± 0.49%). The GMI was significantly higher than the given HbA1c when HbA1c was below 8.0% (all P < .001). The discordance was the highest at 0.9% for lower HbA1c values (5.0%-5.9%). The proportion of discordance >0.5% improved from 60.1% to 30.9% when using the revised GMI equation in G6 profiles. In FL profile, the overall mean difference between GMI and HbA1c was 0 (P = .966). The GMI was significantly lower by 0.9% than HbA1c of 9.0% to 9.9% and higher by 0.5% in HbA1c of 5.0% to 5.9% (all P < .001). The GMI is overestimated in G6 users, particularly those with well-controlled diabetes, but the GMI and HbA1c discordance improved with a revised equation from the observed data. The FL profile showed greater discordance for lower HbA1c levels or higher HbA1c levels.

Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors for the treatment of diabetes mellitus in liver transplant recipients.

To investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors in liver transplant (LT) recipients with diabetes. A single-centre, retrospective analysis of prospectively collected data from an LT recipient database (1990-2023) was conducted. We included adults with pre-existing diabetes and post-transplant diabetes, newly started on GLP-1RAs and/or SGLT2 inhibitors after LT. Metabolic and biochemical parameters and outcomes were collected for up to 12 months after starting medications and were compared to those in patients receiving dipeptidyl peptidase-4 (DPP-4) inhibitors. Statistical analysis included descriptive statistics and linear mixed models. We included participants on GLP-1RAs (n = 46), SGLT2 inhibitors (n = 87), combination therapy (n = 12), and a DPP-4 inhibitor comparator (n = 217). Both GLP-1RAs and combination therapy decreased mean glycated haemoglobin (HbA1c) levels, and combination therapy remained significant when adjusted for DPP-4 inhibitor treatment (-3.5%, 95% CI [-6.1, -0.95]; p = 0.0089) at 12 months. All three groups had significant decreases in mean weight and body mass index, but these remained significant in the GLP-1RA (-5.2 kg, 95% CI [-8.7, -1.7], p = 0.0039 and 1.99 kg/m2, 95% CI [-3.4, -0.6], p = 0.0048) and combination therapy groups (-5.4 kg, 95% CI[-10.5, -0.36], p = 0.04 and -3.4 kg/m2, 95% CI [-5.5, -1.3], p = 0.0015) when adjusted for DPP-4 inhibitor treatment at 12 months. Alanine aminotransferase levels decreased with GLP-1RA and combination therapy. There were two (1.4%) cases of graft rejection. We found that GLP-1RAs, SGLT2 inhibitors, and their combination, led to significant weight loss in LT recipients with diabetes. Combination therapy, in particular, lowered HbA1c and alanine aminotransferase levels compared to DPP-4 inhibitors. Further studies are needed to assess long-term safety and efficacy.

Factors Associated with High-Risk Plaque Characteristics Among Patients with Medium to Severe Carotid Artery Stenosis

ObjectiveThere has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis (CAS). This study aims to identify potential risk factors associated with high-risk carotid plaques. MethodsThis is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, NASCET criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography (MRA) at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (Types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage (IPH) and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated. ResultsA total of 62 patients (mean age: 68.7+/-9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81%±13.53%. In multivariate regression analysis, CRP > 2mg/l was strongly associated with symptomatic stenosis (OR=9.92 [1.12-88.178]; P=0.039), and low HDL levels (<1200mmol/l) were associated with lipidic/necrotic plaque core (OR=16.88 [1.10-259.30]; P=0.043). Low HDL levels (OR=7.22 [1.00-51.95], P=0.049) and HbA1c >7% (OR=0.08 [0.01-0.93], P=0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR=14.26 [1.21-168.34], P=0.035) was associated with Type V plaques. ConclusionsThis preliminary study has revealed some potential risk factors associated with unstable carotid plaques. This data could help the future development of prognostic models in order to early detect patients that could benefit from further intervention.

Role of anagliptin, a dipeptidyl peptidase-4 inhibitor, in managing type 2 diabetes: A systematic review and meta-analysis.

No comprehensive meta-analysis has examined and consolidated the effectiveness and safety of anagliptin in treating type 2 diabetes mellitus (T2D). To bridge this knowledge gap, we undertook this meta-analysis. Randomized controlled trials involving patients with T2D receiving anagliptin were sought after through electronic databases. The control arm consisted of either an active comparator (active control group [ACG]) or a placebo (passive control group [PCG]). The primary outcome was glycated hemoglobin (HbA1c), with secondary outcomes including fasting plasma glucose (FPG) and lipid profiles and adverse events. From the 226 articles first examined, 10 randomized controlled trials with 970 participants were analyzed. Reductions in HbA1c (mean difference [MD]: -0.03%, 95% confidence interval [CI]: -0.14 to 0.14, P = .51, I2 = 9%) and FPG (MD: 0.03 mmol/L, 95% CI: -0.30 to 0.35, P = .87, I2 = 42%) were similar in the anagliptin group and ACG. Anagliptin reduced FPG better than placebo (MD: -1.25 mmol/L, 95% CI: -1.87 to -0.64, P < .0001, I2 = 0%). Sufficient data were unavailable to analyze the HbA1c lowering with anagliptin versus placebo. Among the lipid parameters, changes in total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B48, and apolipoprotein B100 were identical between the anagliptin and control groups (PCG and ACG). Anagliptin was better than ACG at lowering low-density lipoprotein cholesterol but not as good at lowering triglyceride. Adverse events were infrequent and similar in the anagliptin and control groups (PCG and ACG). Anagliptin positively affects glucose control and is safe for managing T2D. Its low-density lipoprotein cholesterol-lowering effect warrants further investigation.

Positive parental history of diabetes is associated with early diagnosis, better dietary compliance, and glycemic control among type 2 diabetes patients in southern Sri Lanka

BackgroundParental history of diabetes is an established risk factor for type 2 diabetes mellitus (T2DM). There is limited data on the association of parental history with the prevalence of T2DM in Sri Lanka. The study aims to examine the prevalence and correlation of parental history and factors such as the onset age, glycaemic control, and self-reported dietary compliance among T2DM patients. With a rising incidence of T2DM in Sri Lanka, understanding the impact of parental history on age at diagnosis and glycemic control can aid in targeted screening and interventions.MethodsA cross-sectional study was carried out on 500 T2DM patients attending a diabetes clinic in Galle, the capital of Southern Sri Lanka with a multiethnic population. Convenient sampling strategy was followed in the recruitment process and a questionnaire-based method was used to collect the data. All the collected data was analysed using SPSS V 25.0.Results51.2% had a parental history of T2DM, and those with a positive parental history were diagnosed six years earlier than those with a negative parental history (p < 0.001). A significant correlation between parental history and gestational diabetes mellitus (GDM) was observed (p < 0.001). Patients with a parental history reported better dietary adherence (p < 0.001). Binary logistic regression analysis revealed patients with positive parental history had significantly lower HbA1C (p = 0.003, OR = 0.748).ConclusionT2DM patients with a parental history showed significant association with early diabetes onset, GDM, better glycemic control, and dietary adherence.

Inhibition of dynamin-related protein 1-filamin interaction improves systemic glucose metabolism.

Maintaining mitochondrial quality is attracting attention as a new strategy to treat diabetes and diabetic complications. We previously reported that mitochondrial hyperfission by forming a protein complex between dynamin-related protein (Drp) 1 and filamin, mediates chronic heart failure and cilnidipine, initially developed as an L/N-type Ca2+ channel blocker, improves heart failure by inhibiting Drp1-filamin protein complex. We investigated whether cilnidipine improves hyperglycaemia of various diabetic mice models. Retrospective analysis focusing on haemoglobin A1c (HbA1c) was performed in hypertensive and hyperglycaemic patients taking cilnidipine and amlodipine. After developing diabetic mice by streptozotocin (STZ) treatment, an osmotic pump including drug was implanted intraperitoneally, followed by weekly measurements of blood glucose levels. Mitochondrial morphology was analysed by electron microscopy. A Ca2+ channel-insensitive cilnidipine derivative (1,4-dihydropyridine [DHP]) was synthesized and its pharmacological effect was evaluated using obese (ob/ob) mice fed with high-fat diet (HFD). In patients, cilnidipine was superior to amlodipine in HbA1c lowering effect. Cilnidipine treatment improved systemic hyperglycaemia and mitochondrial morphological abnormalities in STZ-exposed mice, without lowering blood pressure. Cilnidipine failed to improve hyperglycaemia of ob/ob mice, with suppressing insulin secretion. 1,4-DHP improved hyperglycaemia and mitochondria abnormality in ob/ob mice fed HFD. 1,4-DHP and cilnidipine improved basal oxygen consumption rate of HepG2 cells cultured under 25 mM glucose. Inhibition of Drp1-filamin protein complex formation becomes a new strategy for type 2 diabetes treatment.

Association between Controlled and Uncontrolled DM and Prognosis of Critically ill Patients with Sepsis

Abstract Background In patients with sepsis, an inflammatory response can lead to destruction of the glycocalyx. These alterations cause the progression of organ dysfunction. Destruction of the glycocalyx can also occur in chronic hyperglycemia. Glycated hemoglobin (HbA1c) is a reliable marker of premorbid hyperglycemia. Aim of Work to investigate the association between HbA1c level including the difference between controlled and uncontrolled diabetes mellitus at admission and the degree of organ dysfunction progression 5 days after admission and ICU mortality. Patients and Methods This is a retrospective observational study that included 50 critically ill diabetic patients suffering from sepsis, conducted at the Intensive Care Department, Ain Shams University Hospital. The study design was approved by Ain Shams Faculty of Medicine’s Ethical Committee. All fifty patients were categorized as being diabetic suffering from sepsis into two groups: Group (A): included 25 patients with HBA1C 7% or below. Group (B): included 25 with HBA1C above 7%. Results HbA1C, procalcitonin, ALT, AST and lactic acid were significantly higher in group B compared to group A (P values &amp;lt;0.05) while PLT count was significantly higher in group A compared to group B (P value&amp;lt;0.001). Glucose, CRP and ALT were insignificantly different between the studied groups. Regarding urine analysis, number of patients who had acetone in urine was significantly higher in group B (with HbA1C &amp;gt; 7%) compared to group A (with HbA1C ≤ 7), therefore all those patients were diagnosed as DKA patients and needed insulin. Norepinephrine and Terlipressin use was significantly higher in group B compared to group A (P value = 0.022, 0.007) while epinephrine, dobutamine and dopamine use was insignificantly different between the two groups. Hemodialysis was significantly higher in patients with higher HbA1C level &amp;gt; 7% compared to those with lower HbA1C level (P value = 0.016), while ventilator use was comparable between the two groups. Within 5 days of ICU admission, the incidence of organ dysfunction was significantly higher in patients with higher HbA1C &amp;gt;7% compared to those with lower level of HbA1C (P value = 0.041). Mortality was significantly higher within significantly shorter time in patients with higher HbA1C &amp;gt;7% compared to those with lower level of HbA1C (P value = 0.002, 0.04 respectively). HbA1C can significantly predict the severity of organ dysfunction with AUC of 0.749 (P value &amp;lt;0.001), at cut off &amp;gt;6.9%, HbA1C is a significant predictor for organ dysfunction severity with sensitivity of 94.74%, specificity of 54.84%, PPV of 56.2% and NPV of 94.4%. Conclusion The most common causes of sepsis in ICU patient were pulmonary sepsis followed by urinary tract sepsis. Norepinephrine and terlipressin use was significantly higher in uncontrolled diabetes. Most of patients with uncontrolled diabetes were on hemodialysis while the ventilation use was comparable between the studied groups. Patients with non-controlled diabetes had higher incidence of organ dysfunction and mortality. Age, HbA1C, procalcitonin, PLT and lactic acid were significant predictors for the severity of organ dysfunction within 5 days of ICU admission. We concluded that HbA1C could predict the severity of organ dysfunction.

Possible pitfalls in the prediction of weight gain in middle-aged normal-weight individuals: Results from the NDB-K7Ps-study-2

BackgroundThe prevalence of obesity has not decreased worldwide and obesity-related morbidities have been increasing steadily. However, few studies have investigated factors contributing to weight gain in normal-weight individuals. Thus, in this community-based cohort study, we aimed to investigate factors contributing to weight gain in normal-weight participants. MethodsClinical variables and 10 % increase in weight over 10 years (10 %IBW10Y) were retrospectively investigated in apparently healthy 615,077 normal-weight (body mass index (BMI) 21.0–24.9 kg/m2) participants aged 40–64 years who had regularly undergone health checkup. Machine learning and logistic regression analysis (nested case-control study) were used to predict 10 %IBW10Y. ResultsIn total, 6.8 % of men and 8.9 % of women had 10 %IBW10Y (P < 0.0001). The prevalence of obesity (BMI ≥25.0 kg/m2) after 10 years and weight gain were higher in participants with 10 %IBW10Y (72.3 %, 8.9 kg) (case-group) versus those without 10 %IBW10Y (11.5 %, −0.4 kg) (control-group), respectively. Machine learning showed positive contributing factors to 10 %IBW10Y were, in descending order, age early 40 s, current smoking, female sex, low serum triglyceride (≤59 mg/dL), and low glycated hemoglobin (HbA1c) (≤4.9 %). Age early 60 s, non-smoking, male sex, high triglyceride (≥200 mg/dL), and HbA1c 6.0 %−6.9 % were negative contributing factors. Logistic regression analysis showed similar results except for high HbA1c (≥7.5 %) as a positive contributing factor. ConclusionsIn middle-aged individuals with normal weight who undergo regular health check-ups, certain favorable features (female sex, low triglyceride, and low HbA1c), as well as smoking habits that are subject to change in the future, which could lead to weight gain, may be overlooked.250 ＜250 words

Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management.

Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates. (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations. Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations. All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations. Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients' health, expenditure and quality of life. ClinicalTrials.gov NCT01144338 and NCT00790205.

Polygenic subtype identified in ACCORD trial displays a favorable type 2 diabetes phenotype in the UKBiobank population

IntroductionWe previously identified a genetic subtype (C4) of type 2 diabetes (T2D), benefitting from intensive glycemia treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Here, we characterized the population of patients that met the C4 criteria in the UKBiobank cohort.Research design and methodsUsing our polygenic score (PS), we identified C4 individuals in the UKBiobank and tested C4 status with risk of developing T2D, cardiovascular disease (CVD) outcomes, and differences in T2D medications.ResultsC4 individuals were less likely to develop T2D, were slightly older at T2D diagnosis, had lower HbA1c values, and were less likely to be prescribed T2D medications (P < .05). Genetic variants in MAS1 and IGF2R, major components of the C4 PS, were associated with fewer overall T2D prescriptions.ConclusionWe have confirmed C4 individuals are a lower risk subpopulation of patients with T2D.

The association between glycated hemoglobin levels and long-term prognosis in patients with diabetes and triple-vessel coronary disease across different age groups: A cohort study

AimOur study aimed to investigate the correlation between glycated hemoglobin (HbA1c) and adverse prognostic events in patients with diabetes and triple-vessel coronary disease (TVD). MethodsThis study ultimately included 2051 patients with TVD and diabetes. Patients were categorized into five groups based on their HbA1c levels: < 6.0 %, 6.0–6.4 %, 6.5–6.9 %, 7.0–7.9 %, and ≥ 8.0 %. The primary endpoint was all-cause death, and the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). ResultsThe median follow-up time was 5.88 years. During this period, a total of 323 (15.7 %) all-cause deaths and 537 (26.2 %) MACCEs were recorded. The relationship between HbA1c and the risk of endpoint events showed a J-shaped pattern, with the lowest risk observed between 6.0 % and 6.4 %. Further analysis revealed a significant interaction between HbA1c and age. In the subgroup with age < 70 years, as HbA1c increased, the risk of endpoint events gradually rose. While in the subgroup with age ≥70 years, there was an L-shaped relationship between HbA1c and endpoint events, with the highest risk observed in patients with HbA1c < 6.0 %. ConclusionOur study revealed variations in the relationship between HbA1c levels and endpoint events among patients with TVD and diabetes of different ages. In younger patients, elevated HbA1c levels were associated with a higher risk of death and MACCE, while in older patients, excessively low HbA1c levels (HbA1c < 6 %) were linked to a higher risk of death and MACCE.

Responses to Basal Insulin Glargine (300U/mL and 100U/mL) with or Without Pre-prandial Insulin in Pre-treated Subphenotypes of Type2 Diabetes: Insights from a Post Hoc Analysis.

This study aimed to evaluate glycemic outcomes in subphenotypes of type2 diabetes (T2D) with HbA1c > 7.0%, previously on basal insulin (pre-BI) alone (≥ 42U/day) or on basal-bolus therapy (pre-BB), and who were switched to either basal insulin glargine 300U/mL (IGlar-300) or 100U/mL (IGlar-100), with or without pre-prandial insulin. Participants from EDITION2 (pre-BI, n = 785), and EDITION1 (pre-BB, n = 792) trials were assigned retrospectively to subphenotypes of T2D: severe insulin deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity diabetes (MOD), and severe insulin resistant diabetes (SIRD). Key efficacy and safety parameters were analyzed at baseline, and after 26weeks, for IGlar-300 and IGlar-100 pooled groups according to subphenotypes. Outcomes were also compared with insulin-naïve subphenotypes on oral antihyperglycemic drugs (OADs) from the EDITION3 trial (pre-OAD, n = 858). Pre-BI and pre-BB treated subphenotypes with SIDD had a higher mean HbA1c (8.9% and 9.1%) at baseline compared to those of MARD (7.7% and 7.8%) and MOD (8.1% and 8.2%) and after 26weeks remained above target HbA1c (7.7% and 8.0%) despite mean glargine doses of 0.7 to 1.0U/kg/day and pre-prandial insulin use in the pre-BB SIDD subgroup. Pre-BB treated individuals with MARD and MOD achieved lower HbA1c levels (6.9% and 7.2%) than the pre-BI groups (7.3% and 7.5%) despite similar mean FPG levels (123-130mg/dL). Only 19-22% of participants with SIDD achieved HbA1c < 7.0% compared to 33-51% with MARD and MOD, respectively. Pre-BI and pre-BB treated subphenotypes experienced more hypoglycemia than pre-OAD treated subphenotypes. Individuals with T2D assigned post hoc to the SIDD subphenotype achieved suboptimal glycemic control with glargine regimens including basal-bolus therapy, alerting clinicians to improve further diabetes treatment, particularly post-prandial glycemic control, in individuals with SIDD.