Metabolic studies in unaffected co-twins of non-insulin-dependent diabetics.

Barnett, Anthony; Spiliopoulos, A.; Pyke, David A.; Stubbs, W. A.; Burrin, Jacky M.; Alberti, K. G. M. M.

doi:10.1136/bmj.282.6277.1656

Cited by 75 publications

(34 citation statements)

References 10 publications

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“…In a cross-sectional study (Study 1) changes in glucose tolerance occurred without changes in other intermediary metabolites or insulin. This contrasts with studies of non-diabetic patients at risk of non-insulin-dependent diabetes which showed that these patients can have changes in both glucose and intermediary metabolites [6,7]. The twins who remain non-diabetic did not, as a group, show any changes in either intermediary metabolites or insulin levels; one of these twins from Study i had impaired glucose tolerance.…”

Section: Discussioncontrasting

confidence: 66%

“…These observations suggest that clinical diabetes is preceded by detectable metabolic changes presumably due to Beta cell dysfunction. Minor Beta cell dysfunction can be associated with extensive changes in intermediary metabolism other than glucose; such changes have been found in nondiabetic identical twins and children of non-insulin-dependent diabetic patients both of whom were at high risk of developing diabetes [6,7]. Similar changes in intermediary metabolism could occur in twins at risk of insulin-dependent diabetes mellitus.…”

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confidence: 95%

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Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins

et al. 1990

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Summary. Non-diabetic identical twins of insulin-dependent diabetic patients were studied within five years of the diagnosis of their index twin in order to determine whether changes in intermediary metabolism precede the onset of insulin-dependent diabetes mellitus. Two studies were performed: a cross-sectional study of 12 non-diabetic twins and a prospective study of a separate group of 41 non-diabetic twins. Of the 12 twins tested in the cross-sectional study six developed insulin-dependent diabetes and six did not; the six who developed diabetes were given an oral glucose load a mean of 10 months before diagnosis; they then had normal fasting blood glucose levels but worse glucose tolerance than control subjects (120 min post-load (mean + SD) blood glucose 8.5 _+ 3.5 vs 4.9 + 0.9 mmol/1 respectively, p < 0.05). However, blood lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate and serum insulin levels were similar. In contrast, the six twins in this cross-sectional study who did not develop diabetes and are now unlikely to do so, as a group, had no significant changes compared with the control subjects though one had impaired glucose tolerance. To determine the predictire value of impaired glucose tolerance a separate group of 41 non-diabetic twins was studied prospectively for 8 to 22 years having a total of 147 glucose tolerance tests in' this period; in this group six developed diabetes. Eight of the 41 had impaired glucose tolerance; impaired glucose tolerance was found in four of the six who developed diabetes as compared with only four of the 35 who did not (p < 0.01). Impaired glucose tolerance in these non-diabetic identical twins had a positive predictive value of 33% for developing diabetes. The four twins with impaired glucose tolerance who remain nondiabetic now have normal glucose tolerance. We conclude that impaired glucose tolerance may precede the onset of insulin-dependent diabetes mellitus by many months but the change does not specifically predict the disease even in identical twins of diabetic patients. These observations are consistent with the possibility that in some twins the disease process can occur yet remit without leading to diabetes.

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Section: Discussioncontrasting

confidence: 66%

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confidence: 95%

Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins

et al. 1990

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“…Follow-up questionnaires have been sent in 1981, 1990(Kaprio, 2013, and the twins have been linked to national medical registers (hospital discharge, medication, and cause-of-death data). Information from these registers, hospital charts, and questionnaire surveys were used to identify and classify twins with diabetes and the type of diabetes.…”

Section: The Finnish Twin Cohort Study (Ftcs)mentioning

confidence: 99%

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium

et al. 2015

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Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

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“…If the increased lactate production per fat cell under hyperinsulinemic conditions, as demonstrated in this study, has any relation to the increased risk of type 2 diabetes in individuals with enlarged subcutaneous abdominal fat cell size (58), then it needs to be evaluated in future studies. However, lactate elevation could possibly be a forerunner of or causative factor in (22-24) the development of carbohydrate intolerance and type 2 diabetes (12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, epidemiological data have shown that elevated plasma lactate is an independent risk factor for developing type 2 diabetes (11); moreover, in previous studies (12)(13)(14), plasma lactate was either slightly increased or similar in the relatives of type 2 diabetic patients. It is well known that insulin-resistant obese subjects exhibit increased circulating lactate concentrations (15,16).…”

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confidence: 99%

Increased Lactate Release per Fat Cell in Normoglycemic First-Degree Relatives of Individuals With Type 2 Diabetes

2001

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The aim of this study was to examine subcutaneous lactate production in the relatives of individuals with type 2 diabetes. Therefore, we recruited seven healthy first-degree relatives of type 2 diabetic patients and seven pairwise, matched, healthy control subjects without any heredity for diabetes. All subjects were studied with a euglycemic insulin clamp at ϳ600 pmol/l, abdominal subcutaneous microdialysis, and 133 Xe clearance. Furthermore, a subcutaneous needle biopsy was performed to determine fat cell size. In the fasting state, interstitial lactate was 40% higher in relatives than in control subjects (P ‫؍‬ 0.043), but net lactate production was similar in both groups. However, during the insulin clamp, interstitial lactate (2.50 ؎ 0.29 vs. 1.98 ؎ 0.26 mmol/l, P ‫؍‬ 0.018), interstitial-arterial lactate concentration difference (1.08 ؎ 0.30 vs. 0.53 ؎ 0.24 mmol/l, P ‫؍‬ 0.028), and net lactate release per fat cell (10.9 ؎ 3.7 vs. 2.8 ؎ 1.3 fmol ⅐ cell -1 ⅐ min -1 , P ‫؍‬ 0.018) were increased in the relatives. We conclude that first-degree relatives of type 2 diabetic patients may have an enhanced net lactate release per fat cell in abdominal subcutaneous tissue. This could suggest a pathological regulation in adipose tissue that is of importance for the metabolic defects known in type 2 diabetic relatives.

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Metabolic studies in unaffected co-twins of non-insulin-dependent diabetics.

Cited by 75 publications

References 10 publications

Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins

Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium

Increased Lactate Release per Fat Cell in Normoglycemic First-Degree Relatives of Individuals With Type 2 Diabetes

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