Month: March 2025

Carnitine supplementation improves insulin sensitivity and skeletal muscle acetylcarnitine formation in patients with type 2 diabetes

Abstract
Aim/Hypothesis
Recently, we reported that increasing free carnitine availability resulted in elevated skeletal muscle acetylcarnitine concentrations and restored metabolic flexibility in individuals who have impaired glucose tolerance. Metabolic flexibility is defined as the capacity to switch from predominantly fat oxidation while fasted to carbohydrate oxidation while insulin stimulated. Here we investigated if carnitine supplementation enhances the capacity of skeletal muscle to form acetylcarnitine and thereby improves insulin sensitivity and glucose homeostasis in patients with type 2 diabetes (T2DM).
Methods
Thirty-two patients followed a 12-week L-carnitine treatment (2970 mg/day, orally). Insulin sensitivity was assessed by a two-step hyperinsulinemic-euglycemic clamp. In vivo skeletal muscle acetylcarnitine concentrations at rest and post-exercise (30 min, 70% W
max) and intrahepatic lipid content (IHL) were determined by proton magnetic resonance spectroscopy (1H-MRS). All measurements were performed before and after 12 weeks of carnitine supplementation.
Results
Compliance with the carnitine supplementation was good (as indicated by increased plasma-free carnitine levels (p < 0.01) and pill count (97.1 ± 0.7%)). Insulin-induced suppression of endogenous glucose production (31.9 ± 2.9 vs. 39.9 ± 3.2%, p = 0.020) and peripheral insulin sensitivity (Δ rate of glucose disappearance (ΔRd): 10.53 ± 1.85 vs. 13.83 ± 2.02 μmol/kg/min, p = 0.005) improved after supplementation. Resting (1.18 ± 0.13 vs. 1.54 ± 0.17 mmol/kgww, p = 0.008) and post-exercise (3.70 ± 0.22 vs. 4.53 ± 0.30 mmol/kgww, p < 0.001) skeletal muscle acetylcarnitine concentrations were both elevated after carnitine supplementation. Plasma glucose (p = 0.083) and IHL (p = 0.098) tended to be reduced after carnitine supplementation.
Conclusion
Carnitine supplementation improved insulin sensitivity and tended to lower IHL and fasting plasma glucose levels in patients with type 2 diabetes. Furthermore, carnitine supplementation increased acetylcarnitine concentration in muscle, which may underlie the beneficial effect on insulin sensitivity.

Disparities in heart failure deaths among people with diabetes in the United States: 1999–2020

Abstract
Aims
Heart failure is a leading cause of mortality in the United States, with significant disparities in its burden, particularly among underserved populations. A similar pattern exists for diabetes, but less is known about the mortality impact of these two comorbid conditions. This study aims to examine the risk of death from heart failure among people with diabetes, focusing on socio-demographic disparities.
Materials and Methods
We analysed data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death Database, examining patterns of heart failure deaths in which diabetes was a contributing cause. Our analysis was stratified by socio-demographic variables, including race, ethnicity and geography, and we also explored trends over time.
Results
Between 1999 and 2020, there were 82 617 deaths from heart failure in which diabetes was a contributing cause, with an age-adjusted mortality rate of 32.04 deaths per 1 000 000 individuals. The death rate increased by 2.18% during the study period. Death rates were higher among Black Americans compared with White Americans (age-adjusted mortality rate ratio = 1.51, 95% confidence interval: 1.49–1.53), with disparities growing over time (a 10.75% increase for Black Americans vs. a 1.11% increase for White Americans).
Conclusions
Deaths from comorbid heart failure and diabetes are increasing in the United States, with significant and worsening disparities, particularly among minorities. Urgent action is needed to reduce heart failure mortality among people with diabetes, especially in underserved populations.