High prevalence of proliferative retinopathy in diabetic patients with low pancreatic B-cell capacity

Suzuki, Kazuo; Watanabe, Kyoko; Motegi, Tsutomu; Kajinuma, Hiroshi

doi:10.1016/0168-8227(89)90056-9

Cited by 33 publications

(44 citation statements)

References 21 publications

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“…Figure 2 Cumulative incidence of any and specific chronic complications by C-peptide tertiles in 931 type 2 diabetic patients without any complications at baseline. The inconsistencies among previous studies that have evaluated the associations between C-peptide levels and chronic complications in type 2 diabetes may be due to differences in the study designs and populations (12,13,14,15,16,17,21,22,24,25,29); however, these differences again highlight the complexity of these relationships in a disease with a pathophysiology that is still incompletely defined.…”

Section: Discussionmentioning

confidence: 62%

“…Furthermore, the role of C-peptide is not well defined in type 2 diabetes, a disease that is now considered to be a consequence of the reduced b-cell function superimposed on a condition of insulin resistance (11). Some prospective studies have found that residual insulin secretion has a protective effect on microvascular complications (12), while others have failed to find such an association (13,14). However, previous studies have included either patients who were already complicated at baseline (12,13) or a small number of individuals (12,14).…”

Section: Introductionmentioning

confidence: 99%

“…Some prospective studies have found that residual insulin secretion has a protective effect on microvascular complications (12), while others have failed to find such an association (13,14). However, previous studies have included either patients who were already complicated at baseline (12,13) or a small number of individuals (12,14). Finally, no data regarding the association between residual insulin secretion and major outcomes, such as all-cause mortality and mortality due to cardiovascular diseases, are available in type 2 diabetic patients, while a few cross-sectional studies show contrasting data about the association of C-peptide and macrovascular complications (15,16).…”

Section: Introductionmentioning

confidence: 99%

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C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up

Gentile

Castiglione

et al. 2012

European Journal of Endocrinology

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Objective: C-peptide, a cleavage product of insulin, exerts biological effects in patients with type 1 diabetes mellitus, but its role in type 2 diabetes mellitus is controversial. Our aim was to examine the associations between fasting C-peptide levels and all-cause mortality, specific-cause mortality and the incidence of chronic complications in patients with type 2 diabetes. Design: Retrospective cohort study with a median follow-up of 14 years. Methods: A representative cohort of 2113 patients with type 2 diabetes mellitus and a subgroup of 931 individuals from this cohort without chronic complications at baseline from a diabetic clinic were studied. Results: Patients with higher C-peptide levels had higher baseline BMI and triglyceride and lower HDL-cholesterol values. During the follow-up, 46.1% of the patients died. In a Cox proportional hazard model, after multiple adjustments, no significant association was found between the C-peptide tertiles and all-cause mortality or mortality due to cancer, diabetes or cardiovascular diseases. In the subgroup of 931 patients without chronic complications at baseline, the incidence of microvascular complications decreased from the first to the third C-peptide level tertile, while the incidence of cardiovascular disease did not differ. The risks for incident retinopathy (hazard ratio (HR)Z0.33; 95% confidence interval (CI) 0.23-0.47), nephropathy (HRZ0.27; 95% CI 0.18-0.38) and neuropathy (HRZ0.39; 95% CI 0.25-0.61) were negatively associated with the highest C-peptide tertile, after adjusting for multiple confounders. Conclusions: Higher baseline C-peptide levels were associated with a reduced risk of incident microvascular complications but imparted no survival benefit to patients with type 2 diabetes mellitus.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up

Gentile

Castiglione

et al. 2012

European Journal of Endocrinology

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“…Because a risk of DR has been associated with insulin resistance [44] and low beta-cell function [45,46], active vitamin D could induce retinal protection indirectly by inducing beta-cell protection [47], insulin secretion [48±50] and insulin sensitivity [49±51]. Interestingly, at least one report associated the b allele of Bsm I, which shows strong linkage disequilibrium with T allele of Taq I site, with significantly lower serum calcitriol concentrations than control subjects [52], although other studies found the opposite effect [21].…”

Section: Discussionmentioning

confidence: 99%

Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy

et al. 2002

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Neovascularization plays a role in determining the severity of diabetic retinopathy (DR) due to the effects of several angiogenic and growth factors, including vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-1) [1].Chronic hyperglycaemia induces non-severe diabetic retinopathy (DR) in most patients of long duration, but not severe DR in the majority of them, sug- Abstract Aims/hypothesis. Vitamin D, a molecule with antiproliferative, antiangiogenic, antioxidant and immunosuppressive effects, could play a role in the pathogenesis of severe diabetic retinopathy. We examined whether Taq I polymorphism of the vitamin D receptor is involved in the development of severe diabetic retinopathy. Methods. 200 unrelated C-peptide-negative French Type I diabetic patients were randomly selected (male:female, 103:97, age 44.4 12.4 years, diabetes duration: 27.7 10.0 years, BMI: 24.3 3.4 kg/m 2 , HbA 1 c : 8.6 1.3 %). The Taq I site was analysed by PCR followed by digestion with Taq I enzyme. Diabetic retinopathy was assessed by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (preproliferative or proliferative) diabetic retinopathy. Results. Frequency of wild-type genotype TT was lower in patients with severe diabetic retinopathy (n = 27) when compared with control subjects (n = 42, OR = 0.5, p = 0.028). Allele frequencies were not different between patients (T: n = 112 and t: n = 90) and control subjects (T: n = 128, and t: n = 70, p = 0.075). Global c 2 (df = 2): p = 0.064. In subjects with diabetes duration of more than 25 years, TT was lower in severe diabetic retinopathy (n = 14) than control subjects (n = 18, OR = 0.3, p = 0.01). Allele frequencies were different between patients (T: n = 68 and t: n = 66) and control subjects (T: n = 52, OR = 0.5, and t: n = 26, OR = 1.9, p = 0.034). Global c 2 (df = 2): p = 0.024. In subjects with HbA 1 c over 9 %, Tt was higher in patients (n = 28) than control subjects (n = 15, OR = 3.1, p = 0.019). Allele frequencies were not different between patients (T: n = 52 and t: n = 38) and control subjects (T: n = 57, and t: n = 29, p = 0.31). Global c 2 (df = 2): p = 0.035. Conclusion/interpretation. In French Type I (insulindependent) diabetic patients, we demonstrate an association between TT form (VDR) and low risk for severe diabetic retinopathy, especially in patients with long duration, and between Tt variant and high risk for severe diabetic retinopathy in subjects with poor glycaemic control. [Diabetologia (2002) 45: 436±442]

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“…Few DCCT participants reached normal levels of HbA 1c ; however, for those who could approach that goal (i.e., those with values Ͻ7.5%), sustained islet function permitted a nearoptimal outcome (universal benefits in reduced microvascular complications and fewer incidences of severe hypoglycemia). These analyses build upon earlier studies (10,11) by following a larger group of subjects for a longer period of time, as compared with other studies (11)(12)(13), and by more finely categorizing subjects with respect to islet cell function (4,5).…”

Section: Adjustments For Demographic Factors and Glycemic Controlmentioning

confidence: 99%

β-Cell Function and the Development of Diabetes-Related Complications in the Diabetes Control and Complications Trial

et al. 2003

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In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining ␤-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual ␤-cell activity in type 1 diabetes, stimulated (90 min following ingestion of a mixed meal) C-peptide levels at entry in the Diabetes Control and Complications Trial (DCCT) were related to measures of diabetic retinopathy and nephropathy and to incidents of severe hypoglycemia. Based on the analytical sensitivity of the assay (0.03 nmol/l) and study entry criteria, the DCCT subjects were divided into four groups of stimulated C-peptide responses: Յ0.03, 0.04 -0.20, 0.21-0.50 nmol/l at entry, and 0.21-0.50 nmol/l at entry and at least 1 year later (sustained C-peptide secretion). Uniformly in the intensive and partially in the conventional DCCT treatment groups, any C-peptide secretion, but especially at higher and sustained levels of stimulated C-peptide, was associated with reduced incidences of retinopathy (both a single three-step change and a repeated three-step change on the Early Treatment of Diabetic Retinopathy Study [ETDRS] scale at the next 6 month visit) and nephropathy (both albuminuria Ͼ40 mg/24 h once and repeated at the next annual visit). There were also differences in severe hypoglycemia across C-peptide levels in both treatment groups. In the intensively treated cohort there were essentially identical prevalences of severe hypoglycemia (ϳ65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level Ͼ0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of ϳ30%. Therefore, even modest levels of ␤-cell activity at entry in the DCCT were associated with reduced incidences of retinopathy and nephropathy. Also, continuing C-peptide (insulin) secretion is important in avoiding hypoglycemia (the major complication of intensive diabetic therapy).

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High prevalence of proliferative retinopathy in diabetic patients with low pancreatic B-cell capacity

Cited by 33 publications

References 21 publications

C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up

C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up

Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy

β-Cell Function and the Development of Diabetes-Related Complications in the Diabetes Control and Complications Trial

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