Abstract
Aims/hypothesisApparent type 2 diabetes is increasingly reported in lean adult individuals in sub-Saharan Africa. However, studies undertaking robust clinical and metabolic characterisation of lean individuals with new-onset type 2 diabetes are limited in this population. This cross-sectional study aimed to perform a detailed clinical and metabolic characterisation of newly diagnosed adult patients with diabetes in Uganda, in order to compare features between lean and non-lean individuals.MethodsSocio-demographic, clinical, biophysical and metabolic (including oral glucose tolerance test) data were collected on 568 adult patients with newly diagnosed diabetes. Participants were screened for islet autoantibodies to exclude those with autoimmune diabetes. The remaining participants (with type 2 diabetes) were then classified as lean (BMI <25 kg/m2) or non-lean (BMI ≥25 kg/m2), and their socio-demographic, clinical, biophysical and metabolic characteristics were compared.ResultsThirty-four participants (6.4%) were excluded from analyses because they were positive for pancreatic autoantibodies, and a further 34 participants because they had incomplete data. For the remaining 500 participants, the median (IQR) age, BMI and HbA1c were 48 years (39–58), 27.5 kg/m2 (23.6–31.4) and 90 mmol/mol (61–113) (10.3% [7.7–12.5]), respectively, with a female predominance (approximately 57%). Of the 500 participants, 160 (32%) and 340 (68%) were lean and non-lean, respectively. Compared with non-lean participants, lean participants were mainly male (60.6% vs 35.3%, p<0.001) and had lower visceral adiposity level (5 [4–7] vs 11 [9–13], p<0.001) and features of the metabolic syndrome (uric acid, 246.5 [205.0–290.6] vs 289 [234–347] μmol/l, p<0.001; leptin, 660.9 [174.5–1993.1] vs 3988.0 [1336.0–6595.0] pg/ml, p<0.001). In addition, they displayed markedly reduced markers of beta cell function (oral insulinogenic index 0.8 [0.3–2.5] vs 1.6 [0.6–4.6] pmol/mmol; 120 min serum C-peptide 0.70 [0.33–1.36] vs 1.02 [0.60–1.66] nmol/l, p<0.001).Conclusions/interpretationApproximately one-third of participants with incident adult-onset non-autoimmune diabetes had BMI <25 kg/m2. Diabetes in these lean individuals was more common in men, and predominantly associated with reduced pancreatic secretory function rather than insulin resistance. The underlying pathological mechanisms are unclear, but this is likely to have important management implications.Graphical abstract
Highlights
Type 2 diabetes has reached epidemic proportions globally
Despite obesity and overweight being welldocumented risk factors of type 2 diabetes, there is accumulating evidence, from low- and middle-income countries, that type 2 diabetes can develop in lean individuals [3,4,5,6,7,8,9,10]
Most of the evidence on type 2 diabetes in lean individuals has originated from South Asian populations, where diabetes is commonly seen in people with normal BMI
Summary
Type 2 diabetes has reached epidemic proportions globally. In sub-Saharan Africa, it remains a major and rapidly growing problem, posing a significant public health challenge and causing a considerable strain on the healthcare systems [1]. BMI was normal, these individuals typically had increased waist circumferences, WHR, total body and visceral adiposity, and ectopic fat deposition, with a metabolic profile characterised by an atherogenic lipid profile (low HDL-cholesterol, high VLDL-cholesterol and triacylglycerol concentrations) [11,12,13,14,15]. This was suggestive of insulin resistance as the underlying pathogenic mechanism. Recent evidence has shown that beta cell secretory dysfunction may be the primary pathogenic defect in such individuals [6, 7, 11, 12, 15,16,17,18,19]
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