Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol

By E. Lim, K. Hollingsworth, Benjamin S. Aribisala, M. Chen, J. Mathers, R. Taylor. Diabetologia, 2011

1,172 citations recorded by the source corpus.

Aims/hypothesisType 2 diabetes is regarded as inevitably progressive, with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake.MethodsEleven people with type 2 diabetes (49.5 ± 2.5 years, BMI 33.6 ± 1.2 kg/m2, nine male and two female) were studied before and after 1, 4 and 8 weeks of a 2.5 MJ (600 kcal)/day diet. Basal hepatic glucose output, hepatic and peripheral insulin sensitivity and beta cell function were measured. Pancreas and liver triacylglycerol content was measured using three-point Dixon magnetic resonance imaging. An age-, sex- and weight-matched group of eight non-diabetic participants was studied.ResultsAfter 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003). Insulin suppression of hepatic glucose output improved from 43 ± 4% to 74 ± 5% (p = 0.003 vs baseline; controls 68 ± 5%). Hepatic triacylglycerol content fell from 12.8 ± 2.4% in the diabetic group to 2.9 ± 0.2% by week 8 (p = 0.003). The first-phase insulin response increased during the study period (0.19 ± 0.02 to 0.46 ± 0.07 nmol min−1 m−2; p < 0.001) and approached control values (0.62 ± 0.15 nmol min−1 m−2; p = 0.42). Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min−1 m−2). Pancreatic triacylglycerol decreased from 8.0 ± 1.6% to 6.2 ± 1.1% (p = 0.03).Conclusions/interpretationNormalisation of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone. This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Surgery

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Citations in the corpus

Non-Alcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases (2017, positive): “These results have been replicated by other hypocaloric feeding studies (Lazo et al., 2010; Lim et al., 2011).”
Standards of Medical Care in Diabetes—2020 Abridged for Primary Care Providers (2019, background): “factors) identifies individuals who may develop type 1 diabetes (9).”
Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes (2017, background): “After Roux-en-Y gastric bypass several rapid changes have been noted aside from the lower insulin and plasma glucose levels, including lower blood levels of leptin and branched amino acids, higher concentrations of adiponectin and bile acids, and stronger post prandial increases of GLP-1 and of the ”
Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links (2012, positive): “But enforced dietary caloric restriction can still rapidly reduce hepatic steatosis in obese patients (Lim et al., 2011; Petersen et al., 2005).”
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. (2016, background): “Proof-of-concept studies in rodent models of NALFD and T2D demonstrate that mildly increasing hepatic mitochondrial inefficiency can safely reverse hypertriglyceridemia, ectopic lipid-induced (DAG/nPKC) liver and muscle insulin resistance, steatohepatitis, liver fibrosis, and diabetes, offering a no”
Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis (2016, background): “Weight loss improves insulin sensitivity in liver and skeletal muscle (63) and may also reduce pancreatic fat accumulation (64).”
Why Does Obesity Cause Diabetes? (2022, background): “Weight loss has potent effects on insulin action, and even 5% weight loss improves multiorgan (adipose tissue, liver, and skeletal muscle) insulin sensitivity (Lim et al., 2011; Magkos et al., 2016).”
Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans (2011, background): “, 2006), improving insulin sensitivity (Larson-Meyer et al., 2006; Lim et al., 2011), and reducing cardiovascular risk factors (Lefevre et al.”