Effect of Insulin Therapy on Progression of Retinopathy in Noninsulin-dependent Diabetes Mellitus

Roysarkar, TK; Gupta, Amod; Rj, Dash; Dogra, Mohit

doi:10.1016/s0002-9394(14)71452-7

Cited by 48 publications

(29 citation statements)

References 13 publications

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“…This was reported in several large studies [1,2,3,4] and was confirmed in the Diabetes Control and Complications Trial (DCCT) [5,6,7]. The DCCT study showed deterioration of retinopathy in patients with Type 1 diabetes during the first 3 to 12 months with intensive therapy, followed by a beneficial effect, which increased in magnitude over time.…”

Section: Introductionmentioning

confidence: 53%

Long-term progression of retinopathy after initiation of insulin therapy in Type�2 diabetes: an observational study

2004

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Aims/hypothesis. Universal worsening of retinopathy after starting insulin therapy in Type 2 diabetes has been suggested in previous work. Methods. We studied 294 such patients for up to 5 years to evaluate retinal changes and define the factors affecting progression of retinopathy. Yearly retinal photographs were graded using the EURODIAB system. Results. Prior to insulin therapy, 26.2% (77/294) of the patients had minimal non-proliferative diabetic retinopathy (NPDR), 3.7% (n=11) had moderate NPDR and 1% (n=3) had severe NPDR. Over the first 3 years of insulin therapy, significant progression occurred in 36 subjects (12.6%). This comprised 5/193 (2.6%) without any retinopathy at baseline, 22/77 (28.5%) with minimal NPDR and 6/11 with moderate NPDR (54.5%) (χ 2 =56.1, p<0.001). In a control group of 70 patients who remained on oral hypoglycaemic agents, nine patients had significant worsening of retinopathy over 3 years. Over 5 years, 22/127 (17.3%) of patients (9/95 without and 13/32 with retinopathy at baseline [χ 2 =16.2, p<0.001]) had significant progression of retinopathy. Higher baseline HbA 1 c (p=0.002) and lower initial decrease in HbA 1 c (p=0.007) were each independent predictors of greater retinopathy progression over this period. There was no significant worsening of visual acuity in patients whose retinopathy progressed. Conclusions/interpretation. After initiation of insulin treatment in Type 2 diabetes, clinically significant worsening of retinopathy over a 3-year period was uncommon in those with no retinopathy (2.6%) but occurred in 31.8% of patients with any retinopathy at baseline. The risk of serious worsening of retinopathy after insulin therapy is started in all patients with Type 2 diabetes may have been previously overestimated.

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Section: Introductionmentioning

confidence: 53%

Long-term progression of retinopathy after initiation of insulin therapy in Type�2 diabetes: an observational study

2004

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“…A pathologic role for insulin is supported by the finding that pre-diabetic hyperinsulinemia contributes to glomerular hypertrophy (51). Elevated insulin levels that occur with intensive insulin therapy in type 1 or type 2 diabetes have been associated with transient worsening of diabetic retinopathy (52,53); similarly, short-term peaks in insulin may stimulate laminin-␤1 mRNA translation in renal epithelial cells. Thus, recurrent episodes of high glucose and high insulin may stimulate synthesis of small amounts of laminin-␤1, which over time may contribute to significant expansion of matrix in the kidney in type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

High Glucose, High Insulin, and Their Combination Rapidly Induce Laminin-β1 Synthesis by Regulation of mRNA Translation in Renal Epithelial Cells

et al. 2007

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Laminin is a glycoprotein that contributes to renal extracellular matrix expansion in diabetes. We investigated regulation of laminin-␤1 synthesis in murine renal proximal tubular epithelial cells by 30 mmol/l glucose (high glucose), 1 nmol/l insulin (high insulin), and their combination (high glucose؉high insulin), simulating conditions observed during progression of type 2 diabetes. Compared with 5 mmol/l glucose and no insulin (control), high glucose alone, high insulin alone, or high glucose؉high insulin together increased laminin-␤1 chain protein synthesis within 5 min, lasting for up to 60 min with no change in laminin-␤1 mRNA levels. Cycloheximide, but not actinomycin-D, abrogated increased laminin-␤1 synthesis. High glucose, high insulin, and high glucose؉high insulin stimulated phosphorylation of 4E-BP1, a repressor binding protein for eukaryotic initiation factor 4E (eIF4E), that was dependent on activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin. High glucose, high insulin, and high glucose؉high insulin also promoted release of eIF4E from 4E-BP1, phosphorylation of eIF4E, and increase in eIF4E association with eIF4G, critical events in the initiation phase of mRNA translation. High glucose, high insulin, and high glucose؉high insulin increased Erk phosphorylation, which is an upstream regulator of eIF4E phosphorylation, and PD098059, which is a MEK inhibitor that blocks Erk activation, abolished laminin-␤1 synthesis. This is the first demonstration of rapid increment in laminin-␤1 synthesis by regulation of its mRNA translation by cells exposed to high glucose, high insulin, or high glucose؉high insulin. Diabetes 56:476 -485, 2007 I nsulin resistance and hyperinsulinemia are seen early in type 2 diabetes, followed by hyperglycemia, sometimes accompanied by continued elevation of plasma insulin, although insufficient to compensate for metabolic demands (1,2). Whereas the role of hyperglycemia in diabetes-related complications is established, the role of insulin remains unclear. Resistance to insulin actions in tissues in type 2 diabetes is not universal, with kidney and retina remaining sensitive in contrast to liver (3,4). Insulin may have a regulatory role in renal extracellular matrix (ECM) synthesis because renal cortical insulin receptor activation (3) coincides with the onset of accumulation of laminin-␤1, an abundant constituent of the renal ECM (5).Progressive accumulation of ECM proteins in the glomerular mesangium and tubulointerstitium in diabetes involves laminin in addition to type IV collagen and fibronectin (5-7). Laminin is a large heterotrimeric glycoprotein consisting of ␣-, ␤-, and ␥-chains, with the subunit composition varying with compartment of the renal ECM. Thus, the glomerular basement membrane contains ␣5-, ␤2-, and ␥1-chains, whereas the tubular basement membrane contains ␣5/1-, ␤1-, and ␥1-chains (8). Laminin is involved in regulation of glomerular barrier function because mice lacking laminin-␤2 develop severe proteinuria (9). Renal laminin-...

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“…For CSMT, group 1 tended to have a greater HbA1c reduction (−2.9% vs −1.2% of THb, p=0.074) than group Introduction Improvement of glycemic control reduced the risk of development and progression of diabetic retinopathy [1,2]. However, paradoxical worsening of retinopathy after rapid improvement of blood glucose level in both type 1 and type 2 diabetes was also reported in several literatures [3][4][5][6][7][8][9][10][11]. The Diabetes Control and Complication Trial (DCCT) demonstrated that early worsening of retinopathy was observed at 6-and 12-month visits in 13.1% of patients assigned to intensive treatment, and in 7.6% of patients assigned to conventional treatment.…”

Section: Abstractsmentioning

confidence: 99%

The change of macular thickness measured by optical coherence tomography in relation to glycemic control in diabetic patients

Moon

Kim

et al. 2010

Graefes Arch Clin Exp Ophthalmol

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Effect of Insulin Therapy on Progression of Retinopathy in Noninsulin-dependent Diabetes Mellitus

Cited by 48 publications

References 13 publications

Long-term progression of retinopathy after initiation of insulin therapy in Type�2 diabetes: an observational study

Long-term progression of retinopathy after initiation of insulin therapy in Type�2 diabetes: an observational study

High Glucose, High Insulin, and Their Combination Rapidly Induce Laminin-β1 Synthesis by Regulation of mRNA Translation in Renal Epithelial Cells

The change of macular thickness measured by optical coherence tomography in relation to glycemic control in diabetic patients

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