Multimorbidity among Individuals with Diabetes (MAID) in India: A State-Level Analysis of a National Study

Authors: Sailesh Mohan, et al.

This analysis used data from the Longitudinal Aging Study in India (LASI Wave 1) a nationwide survey among adults aged ≥ 18 hears (n=72,250) to assess the burden of multimorbidity among individuals with diabetes (MAID) across different states and regions of India. MAID was defined as self-reported diabetes mellitus along with at least one of the following self-reported conditions: hypertension, heart disease, cancer, chronic obstructive pulmonary disease, tuberculosis, thyroid disorders, stroke, hepatitis B, arthritis, dementia, depression, hearing impairment, hypercholesterolemia, or neuropsychiatric disorders. The study included 8,714 adults with chronic diseases, with a mean (SD) age of 60.5 years (±11.7), and 59.2% were women. The overall prevalence of MAID was 73.6% (95% confidence interval [CI]: 72.0–75.1), indicating that almost every second almost every second individual with diabetes had at least one other chronic disease. The burden varied substantially across states, ranging from 61.9% to 87.6%. The highest prevalence was reported in Jammu & Kashmir (87.6%, MWI: -6.3 (-6.8, -5.8), followed by Karnataka (86.5%, MWI: -6.9 (-9.1, -4.7), while the lowest prevalence was observed in Chhattisgarh (61.9%, MWI: -4.82 (-5.11, -4.53). Compared with residents of central India, the likelihood of MAID was significantly higher among individuals living in the north (odds ratio (OR=1.40; 95% Clearence [CI]: [1.51, 1.71]) , south (1.49[1.25-1.77]) , east (1.44[1.18-1.75]) , west (1.32 [1.08, 1.62]) , and northeast (1.27 [1.01-1.60]) regions.

Overall, the study highlights the high burden of multimorbidity among people with diabetes in India and the considerable variation across states and regions.

Patient-Reported Factors Associated with Inadequate Glycemic Control amongst Younger Adults Newly Diagnosed with Type 2 Diabetes

Authors: Christine Board, et al.

This prospective survey study examined patient-reported factors associated with poor glycemic control during the first year after diagnosis among younger adults with type 2 diabetes (T2D). The study included members of Kaiser Permanente Northern California aged 21–44 years who were recently diagnosed with T2D. Individuals with likely type 1 diabetes or gestational diabetes were excluded. The survey assessed psychosocial factors, care experiences, and sociodemographic characteristics that are not routinely captured in electronic health records, including diabetes distress, depression, life chaos, food insecurity, and preferences regarding healthcare delivery. A total of 610 participants completed the survey. Among the 547 participants with follow-up glycated hemoglobin (HbA1c) data, 32.9% had an HbA1c level greater than 7% at one year after diagnosis, indicating suboptimal glycemic control. Compared with participants who achieved glycemic targets, those with HbA1c levels above 7% were more likely to report food insecurity (38.9% vs. 25.1%; p=0.004), higher life chaos scores (2.58 vs. 2.40; p=0.003), and higher depression scores measured using the Patient Health Questionnaire-8 (PHQ-8) (7.2 vs. 5.8; p=0.005). They were also less likely to feel comfortable with virtual healthcare visits (80.6% vs. 88.0%; p=0.039).

Early glycemic control in younger adults with T2D is shaped by psychosocial and sociodemographic factors, highlighting the importance of delivering holistic, patient‑centered care that addresses social determinants and patient experience from the start.

PCSK9 Inhibitors are Associated with a Lower Risk of Incident Diabetes: A Global Real-World Analysis

Authors: Christine Hsu, et al.

Statins are the primary lipid-lowering therapy, but they are associated with an increased risk of developing diabetes mellitus (DM). This real-world study compared the risk of developing diabetes mellitus (DM) among users of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and other lipid-lowering therapies. Using the TriNetX Global Collaborative Network, researchers identified adults aged ≥50 years with hyperlipidemia and no pre-existing diabetes and compared PCSK9i users with users of statins, ezetimibe, or fenofibrate. After propensity score matching, 20,138 PCSK9i–statin pairs, 23,650 PCSK9i–ezetimibe pairs, and 27,025 PCSK9i–fenofibrate pairs were analyzed. The mean age was 64.4 years, and 49.3% of participants were female. Over 5 years of follow-up, PCSK9i use was associated with a significantly lower risk of incident DM compared with statins (hazard ratio [HR] 0.803; 95% confidence interval [CI]: 0.754–0.855), ezetimibe (HR 0.891; 95% CI: 0.842–0.943), and fenofibrate (HR 0.523; 95% CI: 0.499–0.548).

Overall, PCSK9i therapy was associated with a lower risk of developing diabetes compared with commonly used lipid-lowering agents and may be a metabolically favorable lipid lowering option in older adults with hyperlipidemia and at high risk for DM.

Do First-Trimester Metabolic or Lipid Measures Improve Prediction of GDM and LGA?

Authors: Erin LeBlanc, et al.

This secondary analysis of the GO MOMs study evaluated whether early pregnancy metabolic and lipid measures improve prediction of gestational diabetes mellitus (GDM) or large-for-gestational-age (LGA) births beyond established clinical risk factors and oral glucose tolerance test (OGTT) results. The study included 2,178 pregnant women without preexisting diabetes from 9 US centers. Between 10 and 14 weeks of gestation, participants underwent a 75-g oral glucose tolerance test (OGTT), assessment of insulin sensitivity and β-cell function, and measurement of fasting free fatty acids (FFA) and triglycerides (TG). Prediction models for GDM included clinical factors such as age, BMI, history of GDM or macrosomia and OGTT values to predict GDM at 24–28 weeks, based on the Carpenter–Coustan criteria, in addition to insulin sensitivity, and β-cell function, For LGA prediction, FFA and TG were added to the models. Among participants, 91% completed OGTTs, and 15% developed GDM. Live births occurred in 96% of pregnancies, with 11% resulting in LGA infants. Adding insulin sensitivity or β-cell function measures to models containing clinical factors, with or without OGTT results, did not improve predictive accuracy of GDM. Similarly, neither metabolic measures nor lipid parameters improved the prediction of LGA births.

Overall, early metabolic and lipid measures during pregnancy did not provide additional predictive value for GDM or LGA beyond clinical risk factors and OGTT results.

Variation in A1C in Asian American, Native Hawaiian, and Pacific Islander (AANHPI) Populations with and without Diabetes by Age and BMI: The PANACHE Study

Authors: Yihe Goh Daida, et al.

This study examined mean predicted mean predicted glycated hemoglobin (A1c) levels across Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations and Non-Hispanic White (NHW) adults, assessing differences by age, body mass index (BMI), sex, and diabetes status. The analysis included 792,905 adults aged 30 years or older from Kaiser Permanente Northern California and Hawaii between 2012 and 2022. Participants had no prior cardiovascular disease. A1c levels were evaluated after adjusting for education, income, hypertension, dyslipidemia, smoking, and glucose-lowering medications where applicable. Native Hawaiian and Pacific Islander (NHPI) adults had the highest prevalence of obesity (58%) and dyslipidemia (51%), while Filipino adults had the highest prevalence of hypertension (52%) and diabetes mellitus (35%). Among individuals with diabetes, NHPI adults had the highest adjusted A1c levels across all age and BMI categories. The greatest racial variation in A1c was observed among underweight men with diabetes. Among individuals without diabetes, all AANHPI subgroups had higher adjusted mean A1c levels than NHW adults across normal-weight, overweight, and obese BMI categories and across ages 30–84 years. The highest A1c levels were observed among NHPI, Filipino, and South Asian adults.

Overall, A1c levels differed across AANHPI subpopulations independent of diabetes status, age, sex, and BMI, suggesting the need for population-specific approaches to diabetes screening and management.

Revolutionizing Cardiac Health: Unlocking the Power of Oral Ketones to Boost Cardiac Efficiency, Changes in Insulin Secretion, and Cardiometabolic Outcomes

Authors: Francisca M. Acosta, et al.

Ketone infusion improves ejection fraction (EF) by approximately 6% within 3 hours in patients with T2D and HFrEF. Oral ketones (OKE) have demonstrated similar effects. This study evaluated the effects of chronic OKE ester administration (7 dayson cardiac function in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Twelve patients underwent cardiac magnetic resonance imaging and metabolic assessments at baseline, 3 hours after a single OKE dose, and after 7 days of twice-daily OKE treatment. Participants had a mean body mass index (BMI) of 31±1 kg/m², glycated hemoglobin (HbA1c) of 7.1±0.3%, and ejection fraction (EF) of 42±2% at baseline. OKE administration rapidly increased blood ketone levels to 6.0±0.3 mmol/L at 3 hours and was associated with an increase in EF of 5.9±0.9%. This improvement in cardiac function was maintained after 7 days of treatment. The study also observed increases in C-peptide and insulin levels following OKE administration, suggesting a possible insulin-stimulating effect of ketone bodies.

Overall, short-term OKE administration was well tolerated and was associated with improved cardiac efficiency which appears to be dose-dependent in patients with T2D and HFrEF. The findings also suggest potential insulinogenic effects of ketones, which require further investigation.

C. elegans PDF-1 and the Evolutionary Origin of Incretin-Like Peptides in Treatment of Diet-Induced Obesity

Authors: Yoshiyuki Watanabe, et al.

This study investigated the metabolic effects of pigment dispersing factor-1 (PDF1), a peptide originally identified in Caenorhabditis elegans (C. elegans), which shares structural similarities with glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and their receptors. Researchers evaluated the effects of synthetic PDF1-derived peptides in diet-induced obese mice and in muscle cell experiments at doses of 100 or 200 nmol/kg/day. In mice, treatment with a 37-amino acid PDF1-derived peptide significantly reduced body weight gain (P=0.029) and food intake (P=0.037), although the effects were less pronounced than those observed with tirzepatide. Treatment was also associated with increased expression of brown fat activity markers, including Cidea and Ucp1. PDF1 peptide treatment improved glucose metabolism, resulting in significantly lower plasma glucose levels at 30 and 60 minutes during an oral glucose tolerance test (both P<0.05). Fasting insulin levels and insulin responses during the oral glucose tolerance test were also significantly reduced (both P<0.05). In addition, insulin resistance, assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), was markedly improved and approached normal levels (P<0.001). In cultured C2C12 muscle cells, PDF1-derived peptides significantly increased glucose uptake at concentrations of 10 nM and 100 nM (both P<0.01).

Overall, PDF1-derived peptides produced modest reductions in food intake and weight gain but substantially improved insulin sensitivity and glucose metabolism in preclinical models. These findings indicate that PDF1 may serve as the ancestral precursor of GLP-1 and GIP and could provide a novel framework for the development of new therapeutic agents for diabetes and obesity.

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