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      Phenotypic characterization of nonautoimmune diabetes in adult Ugandans with low body mass index

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          Abstract

          Background:

          Type 2 diabetes is common in relatively lean individuals in sub-Saharan Africa. It is unclear whether phenotypic differences exist between underweight and normal-weight African patients with type 2 diabetes. This study compared specific characteristics between underweight (body mass index <18.5 kg/m 2) and normal-weight (body mass index of 18.5–24.9 kg/m 2) adult Ugandans with new-onset nonautoimmune diabetes.

          Methods:

          We collected the demographic, clinical, anthropometric, and metabolic characteristics of 160 participants with nonobese new-onset type 2 diabetes (defined as diabetes diagnosed <3 months, body mass index <25 kg/m 2, and absence of islet-cell autoimmunity). These participants were categorized as underweight and normal weight, and their phenotypic characteristics were compared.

          Results:

          Of the 160 participants with nonobese new-onset type 2 diabetes, 18 participants (11.3%) were underweight. Compared with those with normal weight, underweight participants presented with less co-existing hypertension (5.6% versus 28.2%, p = 0.04) and lower median visceral fat levels [2 (1–3) versus 6 (4–7), p < 0.001], as assessed by bioimpedance analysis. Pathophysiologically, they presented with a lower median 120-min post-glucose load C-peptide level [0.29 (0.13–0.58) versus 0.82 (0.39–1.50) nmol/l, p = 0.04] and a higher prevalence of insulin deficiency (66.7% versus 31.4%, p = 0.003).

          Conclusion:

          This study demonstrates that nonautoimmune diabetes occurs in underweight individuals in sub-Saharan Africa and is characterized by the absence of visceral adiposity, reduced late-phase insulin secretion, and greater insulin deficiency. These findings necessitate further studies to inform how the prevention, identification, and management of diabetes in such individuals can be individualized.

          Plain language summary

          Type 2 diabetes in underweight Ugandans

          In this study that investigated how type 2 diabetes presents in adult Ugandans with normal body mass index, about one in ten were underweight. Type 2 diabetes in these individuals was characterized by a low prevalence of hypertension, lower body fat levels, and features of reduced insulin production by the pancreas.

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          Most cited references34

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          Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables

          Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.
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            Bioelectrical impedance analysis--part I: review of principles and methods.

            U KYLE (2004)
            The use of bioelectrical impedance analysis (BIA) is widespread both in healthy subjects and patients, but suffers from a lack of standardized method and quality control procedures. BIA allows the determination of the fat-free mass (FFM) and total body water (TBW) in subjects without significant fluid and electrolyte abnormalities, when using appropriate population, age or pathology-specific BIA equations and established procedures. Published BIA equations validated against a reference method in a sufficiently large number of subjects are presented and ranked according to the standard error of the estimate. The determination of changes in body cell mass (BCM), extra cellular (ECW) and intra cellular water (ICW) requires further research using a valid model that guarantees that ECW changes do not corrupt the ICW. The use of segmental-BIA, multifrequency BIA, or bioelectrical spectroscopy in altered hydration states also requires further research. ESPEN guidelines for the clinical use of BIA measurements are described in a paper to appear soon in Clinical Nutrition.
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              The clinical utility of C-peptide measurement in the care of patients with diabetes

              C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. Measurement of insulin secretion using C-peptide can be helpful in clinical practice: differences in insulin secretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This article reviews the use of C-peptide measurement in the clinical management of patients with diabetes, including the interpretation and choice of C-peptide test and its use to assist diabetes classification and choice of treatment. We provide recommendations for where C-peptide should be used, choice of test and interpretation of results. With the rising incidence of Type 2 diabetes in younger patients, the discovery of monogenic diabetes and development of new therapies aimed at preserving insulin secretion, the direct measurement of insulin secretion may be increasingly important. Advances in assays have made C-peptide measurement both more reliable and inexpensive. In addition, recent work has demonstrated that C-peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample (urine C-peptide:creatinine ratio), facilitating measurement in routine clinical practice. The key current clinical role of C-peptide is to assist classification and management of insulin-treated patients. Utility is greatest after 3–5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes. Absent C-peptide at any time confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Journal
                Ther Adv Endocrinol Metab
                Ther Adv Endocrinol Metab
                TAE
                sptae
                Therapeutic Advances in Endocrinology and Metabolism
                SAGE Publications (Sage UK: London, England )
                2042-0188
                2042-0196
                27 May 2024
                2024
                : 15
                : 20420188241252314
                Affiliations
                [1-20420188241252314]Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Plot 51/59 Nakiwogo Road, Entebbe, Uganda
                [2-20420188241252314]Department of Medicine, Uganda Martyrs Hospital Lubaga, Kampala +256, Uganda
                [3-20420188241252314]Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
                [4-20420188241252314]Department of Medicine, Mengo Hospital, Kampala, Uganda
                [5-20420188241252314]Department of Endocrinology, Diabetes, and Metabolism, Christian Medical College Vellore, Vellore, Tamil Nadu, India
                [6-20420188241252314]Albert Einstein College of Medicine, Bronx, NY, USA
                [7-20420188241252314]Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
                [8-20420188241252314]Department of Diabetes and Endocrinology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
                [9-20420188241252314]Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
                [10-20420188241252314]Department of Diabetes and Endocrinology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
                [11-20420188241252314]Department of Non-Communicable Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
                [12-20420188241252314]Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
                [13-20420188241252314]Department of Non-Communicable Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
                Author notes
                Author information
                https://orcid.org/0000-0001-5127-3031
                Article
                10.1177_20420188241252314
                10.1177/20420188241252314
                11131405
                38808009
                74a401b2-bc9f-42f6-9d05-aa6cd26c6157
                © The Author(s), 2024

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 12 October 2023
                : 10 April 2024
                Funding
                Funded by: UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, ;
                Award ID: MC_UP_1204/16
                Funded by: National Institute for Health Research, ;
                Award ID: 17/63/131
                Categories
                Original Research
                Custom metadata
                January-December 2024
                ts1

                atypical diabetes phenotypes,low bmi type 2 diabetes,sub-saharan africa

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