Insulin Deficiency in Non-Insulin-Dependent Diabetes

Temple, RosemaryC; Luzio, Stephen Denis; Schneider, AnneroseE; Carrington, ChristineA; Owens, D. R.; Sobey, W.; Hales, C. N.

doi:10.1016/s0140-6736(89)91306-8

Cited by 329 publications

(149 citation statements)

References 11 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…It is also recognised that elevated circulating proinsulin levels are an important and consistent feature of NIDDM [2][3][4][5], and may represent a specific defect of pancreatic beta-cell function. There is continuing debate as to whether insulin deficiency or insulin resistance represents the primary abnormality which predisposes to the development of NIDDM [6], although it is clear that comparative insulin deficiency is a sine qua non for NIDDM to develop [7].…”

mentioning

confidence: 99%

Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families

et al. 1997

View full text Add to dashboard Cite

Non-insulin-dependent diabetes mellitus (NIDDM) is a complex metabolic condition characterised by both impaired insulin secretion and insulin resistance [1]. It is also recognised that elevated circulating proinsulin levels are an important and consistent feature of NIDDM [2][3][4][5], and may represent a specific defect of pancreatic beta-cell function. There is continuing debate as to whether insulin deficiency or insulin resistance represents the primary abnormality which predisposes to the development of NIDDM [6], although it is clear that comparative insulin deficiency is a sine qua non for NIDDM to develop [7].In an attempt to identify the early fundamental abnormalities, non-diabetic first degree relatives of NIDDM patients have been studied, as they have a 40 % lifetime risk of progressing to diabetes [8]. However, such an approach has so far failed to clarify matters, as some studies have found a principal defect of insulin secretion [9-13], several have suggested that Diabetologia (1997Diabetologia ( ) 40: 1185Diabetologia ( -1190 Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families Summary Non-diabetic first degree relatives of noninsulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North European extraction, and control subjects with no family history of diabetes were matched for age, sex and ethnicity. A 75-g oral glucose tolerance test was conducted and those with newly diagnosed NIDDM were excluded. Basal insulin resistance was determined by homeostasis model assessment (HOMA), and hepatic insulin clearance by C-peptide:insulin molar ratio. Relatives (n = 150) were heavier (BMI: p < 0.0001) than the control subjects (n = 152), and had an increased prevalence of impaired glucose tolerance (15 vs 3 %, p < 0.01). The relatives had increased fasting proinsulin levels and decreased C-peptide levels following the glucose load, while insulin levels were increased at all time points. To examine whether the differences in hormone levels were secondary to the differences in glucose tolerance and adiposity, we studied 100 normal glucose tolerant relatives and control subjects pairmatched for age, sex, waist-hip ratio and BMI. The differences in proinsulin levels were no longer apparent. However, the relatives remained more insulin resistant, and had decreased C-peptide levels and Cpeptide:insulin ratios at all time points. In conclusion, we have identified several metabolic abnormalities in the normal glucose tolerant relatives, and propose that the decreased hepatic insulin clearance helps to maintain normoglycaemia in the face of combined insulin resistance and decreased insulin secretion. [Diabetologie (1997[Diabetologie ( ) 40: 1185[Diabetologie ( -1190

show abstract

mentioning

confidence: 99%

Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Several studies have shown that proinsulin is disproportionately elevated in subjects with NIDDM [10,[37][38][39][40][41]. The ratio of fasting proinsulin/fasting insulin, however, is only minimally elevated in subjects with impaired glucose tolerance in some studies [10,39] and not at all in others [40].…”

Section: Resultsmentioning

confidence: 99%

Are risk factors for conversion to NIDDM similar in high and low risk populations?

1997

View full text Add to dashboard Cite

Numerous studies have shown that Mexican Americans have an increased prevalence [1][2][3][4] and incidence [5] of non-insulin-dependent diabetes mellitus (NIDDM) relative to non-Hispanic whites. The Mexican American population is characterized by increased adiposity [1][2][3][4]6], a more centralized distribution of body fat [6,7], hyperinsulinaemia [8][9][10] and insulin resistance [11,12].Metabolic factors have been shown to be important risk factors for the development of NIDDM. Both insulin resistance [13,14] and hyperinsulinaemia [13,[15][16][17][18][19] have been shown to predict NIDDM. Likewise, decreased insulin secretion in response to various stimuli may predict NIDDM. A low acute insulin response has been found to predict NIDDM in Pima Indians [13], but not in children of two Caucasian diabetic parents [14]. A low 30-min increment in insulin relative to the 30-min increment in glucose (DI 30 /DG 30 ) during an oral glucose tolerance test predicts conversion to NIDDM, especially in subjects with impaired glucose tolerance [20][21][22][23]. A low insulin response 60 min after an intravenous glucose challenge also predicted NIDDM [24,25]. A low 2-h insulin in response to an oral glucose load also Diabetologia (1997) 40: 62-66 Are risk factors for conversion to NIDDM similar in high and low risk populations? Summary Mexican Americans have an increased risk of non-insulin-dependent diabetes mellitus (NIDDM) relative to non-Hispanic whites which is only partially explained by their excess overall obesity and unfavourable body fat distribution. Non-diabetic Mexican Americans have hyperinsulinaemia and insulin resistance relative to non-Hispanic whites. We therefore hypothesized that the insulin resistance might be a more important predictor of NIDDM in high-risk populations characterized by obesity and insulin resistance, while compromised insulin secretion might be a more important risk factor for NIDDM in low-risk populations. We assessed the ability of ethnicity (Mexican American vs non-Hispanic white), age, overall adiposity (body mass index [BMI]), unfavourable body fat distribution (as assessed by waist-to-hip ratio [WHR]), glucose tolerance (impaired glucose tolerance vs normal glucose tolerance), fasting insulin and compromised insulin secretion (as assessed by increment in insulin to the increment in glucose over the first 30 min of an oral glucose tolerance test (DI 30 /DG 30 )) to predict future NIDDM. In the 8-year follow-up of the San Antonio Heart Study, NIDDM developed in 11.7 % (107/914) of Mexican Americans and in 5.0 % (18/362) of nonHispanic whites (p < 0.001). Multivariate predictors of NIDDM by multiple logistic regression analysis included increased age, BMI, WHR, fasting insulin and impaired glucose tolerance and decreased insulin secretion. The strongest independent predictors of NIDDM were high fasting insulin and decreased insulin secretion. These risk factors predicted NIDDM equally well in high and low-risk populations. [Diabetologia (1997) 40: 62-66]

show abstract

“…A large body of evidence supports the role of 32-33 split proinsulin as a marker of insulin resistance. Raised concentrations of split proinsulin in adults have been interpreted as evidence of b-cell dysfunction (Temple et al, 1989) and a risk of impaired glucose tolerance (Hales et al, 1991), but its role as a metabolic marker in infancy has remained poorly understood (Hawdon et al, 1993;Singhal et al, 2003). We found a positive association between the high split proinsulin concentration and the ratio of adipocyte-derived cytokines-leptin and adiponectin-which have been found to correlate with adiposity (Schubring et al, 1999;Mantzoros et al, 2009), and metabolic disorders (Valle et al, 2003;Darendeliler et al, 2009) in newborns and children, and, further, to efficaciously reflect cardio-metabolic risks (Steinberger et al, 2003;Norata et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Serum leptin, adiponectin, 32-33 split proinsulin and intact proinsulin concentrations were assayed on a 1235 AutoDELFIA immunoassay system (PerkinElmer Life Sciences, Boston, MA, USA). All assays were in-house, two-step time-resolved fluorometric assays as previously described (Hales et al, 1991;Semple et al, 2006;Temple et al, 1989), and samples were analysed in duplicate. Samples in which the coefficient of variation of the duplicates was greater than 10% were repeated.…”

Section: Methodsmentioning

confidence: 99%

“…The high 32-33 split proinsulin, a well-characterized predictor of insulin resistance in adults and older children (Temple et al, 1989;Mykkanen et al, 1997;Singhal et al, 2003), was taken as a novel marker of adverse metabolic status in infancy. To further investigate the infants' metabolic status and the usefulness of high split proinsulin in its assessment, waist circumference, skinfold thickness and adipocyte-derived cytokines-leptin and adiponectin- (Shea et al, 2003;Valle et al, 2003;Darendeliler et al, 2009;Corvalan et al, 2010) were taken as secondary outcomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of maternal diet during pregnancy and breastfeeding on infant metabolic programming: a prospective randomized controlled study

et al. 2010

View full text Add to dashboard Cite

Objectives: To evaluate the impact of maternal diet and intensive dietary counselling during pregnancy and breastfeeding on the infant's metabolic status. Subjects/Methods: At the first trimester of pregnancy, 256 women were randomized into a control/placebo group and two dietary counselling groups (diet/probiotics and diet/placebo). The counselling, with double-blind randomization to probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis) or placebo, targeted excessive saturated fat and low fibre consumption. Maternal diet was evaluated repeatedly during pregnancy and postpartum by means of 3 days' food diaries. Metabolic markers, serum 32-33 split and intact proinsulin, leptin/adiponectin ratio, skinfold thickness and waist circumference were measured of 194 healthy infants at the age of 6 months, and the high levels were taken to mirror adverse metabolic status. Results: The proportion of infants with a high 32-33 split proinsulin was significantly lower in dietary counselling with probiotics (n ¼ 6/62, 9.7%) or placebo (n ¼ 7/69, 10.1%) compared with the control/placebo group (n ¼ 17/63, 27.0%). The high split proinsulin was associated with larger skinfold thickness, waist circumference and higher leptin/adiponectin ratio in the infants (Po0.05). With respect to maternal diet during pregnancy, the highest and lowest tertiles of fat intake increased the infant's risk of high split proinsulin, whereas those of butter associated correspondingly with the infant's waist circumference. Further, breastfed infants showed a reduced risk of high split proinsulin and leptin/adiponectin ratio compared with formula-fed infants. Conclusions: Modification of maternal diet during pregnancy and breastfeeding may benefit infant metabolic health. High split proinsulin reflects adverse metabolic status in infancy, which can be improved by early dietary counselling.

show abstract

Insulin Deficiency in Non-Insulin-Dependent Diabetes

Cited by 329 publications

References 11 publications

Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families

Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families

Are risk factors for conversion to NIDDM similar in high and low risk populations?

Impact of maternal diet during pregnancy and breastfeeding on infant metabolic programming: a prospective randomized controlled study

Contact Info

Product

Resources

About