Association of fasting insulin and C peptide with diabetic retinopathy in Latinos with type 2 diabetes

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Abstract

Objective

Residual insulin secretion provides important protection against the development of diabetic retinopathy in type 1 diabetes. The data to support this in type 2 diabetes are unclear. We therefore tested in type 2 diabetes whether markers of residual beta-cell function are associated with the development of diabetic retinopathy, an important microvascular complication of diabetes.

Design

Prospective, cross-sectional, family-based study.

Participants

585 Latino type 2 diabetic participants, ascertained in families via a proband either with known diabetes duration of greater than 10 years and/or with diabetic retinopathy.

Outcome measures

Circulating levels of fasting insulin and C peptide measured and correlated to degree of diabetic retinopathy, assessed by digital fundus photography and graded using the Modified Airlie House Classification and the Early Treatment Diabetic Retinopathy Study scale (range: levels 10–85).

Results

Fasting plasma insulin (β=−0.29; 95% CI −0.38 to −0.20; p<0.0001) and C peptide (β=−0.21; 95% CI −0.30 to −0.13; p<0.0001) concentrations in these diabetic participants were significantly correlated with retinopathy and its degree of severity. This relationship remained significant after adjusting for potential covariates including age, gender, glycosylated hemoglobin, duration of diabetes, blood pressure, and renal function.

Conclusions

These data suggest that residual endogenous insulin secretion is associated with the presence of diabetic retinopathy and its severity in Latinos with familial type 2 diabetes. It remains to be proven whether beta-cell targeted therapies, to maintain beta-cell mass and/or function in addition to glycemic control, will further the goal of preventing diabetic microvascular disease.

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Most cited references 17

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Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group.

(1991)

The modified Airlie House classification of diabetic retinopathy has been extended for use in the Early Treatment Diabetic Retinopathy Study (ETDRS). The revised classification provides additional steps in the grading scale for some characteristics, separates other characteristics previously combined, expands the section on macular edema, and adds several characteristics not previously graded. The classification is described and illustrated and its reproducibility between graders is assessed by calculating percentages of agreement and kappa statistics for duplicate gradings of baseline color nonsimultaneous stereoscopic fundus photographs. For retinal hemorrhages and/or microaneurysms, hard exudates, new vessels, fibrous proliferations, and macular edema, agreement was substantial (weighted kappa, 0.61 to 0.80). For soft exudates, intraretinal microvascular abnormalities, and venous beading, agreement was moderate (weighted kappa, 0.41 to 0.60). A double grading system, with adjudication of disagreements of two or more steps between duplicate gradings, led to some improvement in reproducibility for most characteristics.

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Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group.

John M. Lachin, Saul Genuth, Patricia Cleary … (2000)

Among patients with type 1 diabetes mellitus, intensive therapy (with the aim of achieving near-normal blood glucose and glycosylated hemoglobin concentrations [hemoglobin A1c]) markedly reduces the risk of microvascular complications as compared with conventional therapy. To assess whether these benefits persist, we compared the effects of former and intensive conventional therapy on the recurrence and severity of retinopathy and nephropathy for four years after the end of the Diabetes Control and Complications Trial (DCCT). At the end of the DCCT, the patients in the conventional-therapy group were offered intensive therapy, and the care of all patients was transferred to their own physicians. Retinopathy was evaluated on the basis of centrally graded fundus photographs in 1208 patients during the fourth year after the DCCT ended, and nephropathy was evaluated on the basis of urine specimens obtained from 1302 patients during the third or fourth year, approximately half of whom were from each treatment group. The difference in the median glycosylated hemoglobin values between the conventional-therapy and intensive-therapy groups during the 6.5 years of the DCCT (average, 9.1 percent and 7.2 percent, respectively) narrowed during follow-up (median during 4 years, 8.2 percent and 7.9 percent, respectively, P<0.001). Nevertheless, the proportion of patients who had worsening retinopathy, including proliferative retinopathy, macular edema, and the need for laser therapy, was lower in the intensive-therapy group than in the conventional-therapy group (odds reduction, 72 percent to 87 percent, P<0.001). The proportion of patients with an increase in urinary albumin excretion was significantly lower in the intensive-therapy group. The reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persists for at least four years, despite increasing hyperglycemia.

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Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial.

Melissa Faye Jackson, Michael Steffes, Laura S. Sibley … (2003)

In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining beta-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual beta-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: 40 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 ( approximately 65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level >0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of approximately 30%. Therefore, even modest levels of beta-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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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open Diabetes Res Care

Journal ID (iso-abbrev): BMJ Open Diabetes Res Care

Journal ID (hwp): bmjdrc

Journal ID (publisher-id): bmjdrc

Title: BMJ Open Diabetes Research & Care

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2052-4897

Publication date Collection: 2014

Publication date (Electronic): 24 October 2014

Volume: 2

Issue: 1

Electronic Location Identifier: e000027

Affiliations

[1 ]Shiley Eye Center and Department of Ophthalmology, University of California at San Diego , La Jolla, California, USA

[2 ]Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center , Torrance, California, USA

[3 ]Department of Ophthalmology & Visual Sciences, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin, USA

[4 ]Division of Endocrinology and Metabolism, Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center , Torrance, California, USA

[5 ]Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center , Taipei, Taiwan

[6 ]Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center , Los Angeles, California, USA

Author notes

[Correspondence to ] Prof Eli Ipp; ipp@ 123456labiomed.org

Article

Publisher ID: bmjdrc-2014-000027

DOI: 10.1136/bmjdrc-2014-000027

PMC ID: 4212555

PubMed ID: 25452868

SO-VID: e4839667-49ea-4980-901c-5d90984a9d48

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

History

Date received : 28 February 2014

Date revision received : 12 August 2014

Date accepted : 13 August 2014

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Keywords: retinopathy,insulin,c-peptide

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Keywords: retinopathy, insulin, c-peptide

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Association of fasting insulin and C peptide with diabetic retinopathy in Latinos with type 2 diabetes

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Abstract

Objective

Design

Participants

Outcome measures

Results

Conclusions

Related collections

GLUT4 biology

Most cited references 17

Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group.

Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group.

Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial.

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Cited by 14

Most referenced authors 1,244