Near‐normoglycaemic remission in African‐Americans with Type 2 diabetes mellitus is associated with recovery of beta cell function

McFarlane, Samy I.; Chaiken, Rochelle L; Hirsch, S; Harrington, Patricia; Lebovitz, Harold E.; Banerji, Mary Ann

doi:10.1046/j.1464-5491.2001.00395.x

Cited by 99 publications

(77 citation statements)

References 27 publications

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“…Indeed, after the initial episode of acute insulin deficiency, these patients restore their insulin secretion for a long period of time, helping them to develop normoglycemic remissions lasting for up to 10 years. This pattern of acute and reversible insulin deficiency has already been described by other investigators (6,25). We show that the evolution of ␤-cell dysfunction in non-insulin-dependent ketosis-prone type 2 diabetes is slowly progressive and more similar to that of type 2 diabetes than to that of type 1 diabetes: 10 years after diabetes onset, patients with non-insulin-dependent ketosis-prone type 2 diabetes have lost only 60% of their insulin secretory capacity relative to nonobese control subjects (compared with 61% in type 2 diabetes), and 40% of these patients are still non-insulin dependent (compared with 32.5% in type 2 diabetes).…”

Section: Discussionsupporting

confidence: 77%

Ketosis-Prone Type 2 Diabetes in Patients of Sub-Saharan African Origin

et al. 2004

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Nonautoimmune ketosis-prone diabetic syndromes are increasingly frequent in nonwhite populations. We have characterized a cohort of patients of sub-Saharan African origin who had ketosis-prone type 2 diabetes (n ‫؍‬ 111), type 1 diabetes (n ‫؍‬ 21), and type 2 diabetes (n ‫؍‬ 88) and were admitted to a hospital for management of uncontrolled diabetes. We compared epidemiological, clinical, and metabolic features at diabetes onset and measured insulin secretion (glucagon-stimulated C-peptide) and insulin action (short intravenous insulin tolerance test) during a 10-year follow-up. Ketosis-prone type 2 diabetes shows a strong male predominance, stronger family history, higher age and BMI, and more severe metabolic decompensation than type 1 diabetes. In ketosis-prone type 2 diabetes, discontinuation of insulin therapy with development of remission of insulin dependence is achieved in 76% of patients (noninsulin dependent), whereas only 24% of patients remain insulin dependent. During evolution, ketosisprone type 2 diabetes exhibit specific ␤-cell dysfunction features that distinguish it from type 1 and type 2 diabetes. The clinical course of non-insulin-dependent ketosis-prone type 2 diabetes is characterized by ketotic relapses followed or not by a new remission. Progressive hyperglycemia precedes and is a strong risk factor for ketotic relapses (hazard ratio 38). The probability for non-insulin-dependent ketosis-prone type 2 diabetes to relapse is 90% within 10 years, of whom ϳ50% will become definitively insulin dependent. Insulin sensitivity is decreased in equal proportion in both ketosis-prone type 2 diabetes and type 2 diabetes, but improves significantly in non-insulin-dependent ketosis-prone type 2 diabetes, only after correction of hyperglycemia. In conclusion, ketosis-prone type 2 diabetes can be distinguished from type 1 diabetes and classical type 2 diabetes by specific features of clinical pathophysiology and also by the natural history of ␤-cell dysfunction and insulin resistance reflecting a propensity to glucose toxicity. Diabetes 53: [645][646][647][648][649][650][651][652][653] 2004

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Section: Discussionsupporting

confidence: 77%

Ketosis-Prone Type 2 Diabetes in Patients of Sub-Saharan African Origin

et al. 2004

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“…However, the ability of lifestyle changes to promote β-cell 'recovery' is not universal. By introducing lifestyle changes, including alterations in nutrient content to reduce carbohydrate consumption among patients, McFarlane et al 7 found that roughly half achieved a complete remission of T2D, including a normalisation of β-cell function. Despite a lack of complete functional restoration of β-cells, the remaining patients experienced improvements in insulin sensitivity with reduced reliance on pharmacological therapies.…”

Section: Discussionmentioning

confidence: 99%

“…5 Indeed, these results are sufficiently effective that many scientists and physicians promote such a dietary change as a 'first approach' to managing diabetes. 5 Such a perspective is based on evidence indicating reduced or complete cessation of insulin therapy, 6 as well as improved β-cell function, 7,8 in response to dietary intervention.…”

Section: Introductionmentioning

confidence: 99%

β-Hydroxybutyrate improves β-cell mitochondrial function and survival

Sampson

Lathen

Dallon

et al. 2017

JMH

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Pharmacological interventions aimed at improving outcomes in type 2 diabetes and achieving normoglycaemia, including insulin therapy, are increasingly common, despite the potential for substantial side effects. Carbohydrate-restricted diets that result in increased ketogenesis have effectively been used to improve insulin resistance, a fundamental feature of type 2 diabetes. In addition, limited evidence suggests that states of ketogenesis may also improve β-cell function in type 2 diabetics. Considering how little is known regarding the effects of ketones on β-cell function, we sought to determine the specific effects of β-Hydroxybutyrate (βHB) on pancreatic β-cell physiology and mitochondrial function. βHB treatment increased β-cell survival and proliferation, while also increasing mitochondrial mass, respiration and adenosine triphosphate (ATP) production. Despite these improvements, were unable to detect an increase in β-cell or islet insulin production and secretion. Collectively, these findings have two implications. Firstly, they indicate that β-cells have improved survival and proliferation in the midst of βHB, the circulating form of ketones. Secondly, insulin secretion does not appear to be directly related to apparent improvements in mitochondrial function and cellular proliferation.

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“…Recently, some authors have described this subcategory in other ethnic groups, such as Native Americans and Hispanic Americans (5). The initial manifestation of the diabetes in these cases may be ketoacidosis similar to type 1A diabetes, although the course of the disease is unusual as insulin therapy is initially needed to maintain metabolic control and, after a variable period of time (usually within months), good control can be achieved with either diet or oral agents (5)(6)(7)(8)(9). On the other hand, these patients differ from those with type 1A diabetes because their physical characteristics are more typical of patients with type 2 diabetes; they are often obese or overweight at the time of diagnosis and, in most of the cases, there is a family history of type 2 diabetes (5).…”

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confidence: 99%

Adult-Onset Atypical (Type 1) Diabetes

et al. 2004

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OBJECTIVE—In 1997, the American Diabetes Association proposed two subcategories for type 1 diabetes: type 1A or immunomediated diabetes and type 1B or idiopathic diabetes characterized by negative β-cell autoimmunity markers, lack of association with HLA, and fluctuating insulinopenia. The aim of this study was to examine clinical characteristics, β-cell function, HLA typing, and mutations in maturity-onset diabetes of the young (MODY) genes in patients with atypical type 1 diabetes (type 1 diabetes diagnosed at onset, without pancreatic autoantibodies and fluctuating insulinopenia). RESEARCH DESIGN AND METHODS—Eight patients with atypical type 1 diabetes (all men, 30.7 ± 7.6 years) and 16 newly diagnosed age- and sex-matched patients with type 1A diabetes were studied retrospectively. Islet cell, GAD, tyrosine phosphatase and insulin antibodies, and basal and stimulated plasma C-peptide were measured at onset and after 1 year. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1α and HNF-4α genes were performed from genomic DNA. RESULTS—Atypical patients displayed significantly higher BMI and better β-cell function at onset and after 12 months. Three patients carried protective or neutral type 1 diabetes haplotypes, five patients displayed heterozygosity for susceptible and protective haplotypes, and seven patients showed Aspβ57. We found a nondescribed variant Pro436Ser in exon 10 of the HNF-4α gene in one atypical patient without susceptible haplotypes. CONCLUSIONS—In our population, there are atypical forms of young adult-onset ketosis-prone diabetes initially diagnosed as type 1 diabetes, differing from type 1 diabetes in the absence of β-cell autoimmunity, persistent β-cell function capacity, fluctuating insulin requirements and ketosis-prone episodes, as well as clinical features of type 2 diabetes. Only one subgroup could be strictly classified as having type 1B diabetes. Additional information is still needed to improve our understanding of the mechanisms that finally lead to the disease.

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Near‐normoglycaemic remission in African‐Americans with Type 2 diabetes mellitus is associated with recovery of beta cell function

Cited by 99 publications

References 27 publications

Ketosis-Prone Type 2 Diabetes in Patients of Sub-Saharan African Origin

Ketosis-Prone Type 2 Diabetes in Patients of Sub-Saharan African Origin

β-Hydroxybutyrate improves β-cell mitochondrial function and survival

Adult-Onset Atypical (Type 1) Diabetes

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