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了解新诊断糖尿病的非洲人群中非自身免疫性消瘦型糖尿病的发病机制。

Understanding the pathogenesis of lean non-autoimmune diabetes in an African population with newly diagnosed diabetes.

机构信息

Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.

Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

出版信息

Diabetologia. 2022 Apr;65(4):675-683. doi: 10.1007/s00125-021-05644-8. Epub 2022 Feb 9.


DOI:10.1007/s00125-021-05644-8
PMID:35138411
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8894297/
Abstract

AIMS/HYPOTHESIS: Apparent 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. METHODS: Socio-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/m) or non-lean (BMI ≥25 kg/m), and their socio-demographic, clinical, biophysical and metabolic characteristics were compared. RESULTS: Thirty-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 HbA were 48 years (39-58), 27.5 kg/m (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/INTERPRETATION: Approximately one-third of participants with incident adult-onset non-autoimmune diabetes had BMI <25 kg/m. 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.

摘要

目的/假设:在撒哈拉以南非洲,瘦成年个体中越来越多地报告出现明显的 2 型糖尿病。然而,在该人群中,对新诊断的 2 型糖尿病瘦个体进行稳健的临床和代谢特征描述的研究有限。本横断面研究旨在对乌干达新诊断的成年糖尿病患者进行详细的临床和代谢特征描述,以便比较瘦和非瘦个体之间的特征。

方法:收集了 568 例新诊断糖尿病成年患者的社会人口统计学、临床、生物物理和代谢(包括口服葡萄糖耐量试验)数据。对胰岛自身抗体进行筛查,以排除自身免疫性糖尿病患者。其余参与者(患有 2 型糖尿病)被分为瘦(BMI<25kg/m)或非瘦(BMI≥25kg/m),并比较其社会人口统计学、临床、生物物理和代谢特征。

结果:由于胰岛自身抗体阳性,34 名参与者(6.4%)被排除在分析之外,另有 34 名参与者因数据不完整而被排除。对于其余 500 名参与者,中位(IQR)年龄、BMI 和 HbA 分别为 48 岁(39-58)、27.5kg/m(23.6-31.4)和 90mmol/mol(61-113)(10.3%[7.7-12.5]),女性居多(约 57%)。在 500 名参与者中,160 名(32%)和 340 名(68%)分别为瘦和非瘦。与非瘦参与者相比,瘦参与者主要为男性(60.6%比 35.3%,p<0.001),内脏脂肪水平较低(5[4-7]比 11[9-13],p<0.001),且代谢综合征特征更为明显(尿酸,246.5[205.0-290.6]比 289[234-347]μmol/l,p<0.001;瘦素,660.9[174.5-1993.1]比 3988.0[1336.0-6595.0]pg/ml,p<0.001)。此外,他们表现出明显降低的β细胞功能标志物(口服胰岛素原指数 0.8[0.3-2.5]比 1.6[0.6-4.6]pmol/mmol;120min 血清 C 肽 0.70[0.33-1.36]比 1.02[0.60-1.66]nmol/l,p<0.001)。

结论/解释:大约三分之一新诊断的成年起病非自身免疫性糖尿病患者 BMI<25kg/m。这些瘦个体中的糖尿病更为常见于男性,且主要与胰腺分泌功能降低有关,而非胰岛素抵抗。其潜在的病理机制尚不清楚,但这可能具有重要的管理意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1173/8894297/31401280fe8d/125_2021_5644_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1173/8894297/ff2144ffbd63/125_2021_5644_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1173/8894297/31401280fe8d/125_2021_5644_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1173/8894297/ff2144ffbd63/125_2021_5644_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1173/8894297/31401280fe8d/125_2021_5644_Fig2_HTML.jpg

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