Fasting Glucose and Diabetic Neuropathy
Fasting Glucose and Diabetic Neuropathy
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports that he receives grant/research support from Pfizer and is on the speaker's bureau of Athena Diagnostics.
Synopsis: The risk of peripheral neuropathy gradually increases with a rise in fasting blood sugar, even at levels below that traditionally defined as diabetes mellitus.
Source: Nang EE, Khoo CM, Tai ES, et al. Is there a clear threshold for fasting plasma glucose that differentiates between those with and without neuropathy and chronic kidney disease? The Singapore Prospective Study Program. Am J Epidemiol 2009;169:1454-1462 [E-pub ahead of print, April 30, 2009].
Chronic hyperglycemia results in retinopathy, nephropathy, and peripheral neuropathy. Although initial studies suggested that fasting plasma glucose (FPG) levels above 126 mg/dL resulted in a dramatic rise in the incidence of retinopathy, three large population-based studies subsequently concluded that no clear glycemic threshold differentiates those more likely to develop retinopathy. Rather, the relationship is a continuous one, with a gradual increase in prevalence as FPG rises above normal. What relationship exists between FPG and the development of neuropathy or nephropathy? Is there a threshold effect or is the relationship continual?
Among 11,053 random subjects available from four population-based, cross-sectional surveys conducted in Singapore between 1982 and 1998, including two heart studies and two national health studies, 10,445 were eligible for inclusion in this study of FPG and its microvascular complications, encompassing completion of a questionnaire and submitting to clinical examination and blood studies. After excluding those who could not be contacted (n = 2,673), refused participation (n = 30), did not attend the clinical examination (n = 2,585), or had no FPG level, 5,129 subjects remained for study, of which 3,957 underwent peripheral neuropathy assessment and 4,512 received nephropathy measurements. Sensory testing for neuropathy included measuring vibration perception threshold by neurothesiometer applied to the apex of the big toe and the bilateral medial malleoli, and light-touch testing, using a 5.07 (10-g) monofilament applied to five non-calloused plantar sites on each foot. Urine albumin measurement or estimated glomerular filtration rate (GFR), or both, assessed renal function. Diabetes was defined as FPG > 126 mg/dL or known history of diabetes; neuropathy as a neurothesiometer reading > 25V at any site or monofilament sensory test < 4/5 in either foot; and nephropathy as either albuminuria, defined as a urine albumin/creatinine ratio > 30 mcg/mg, or GFR < 60 mL/minute/1.73 m2. Statistical analysis included chi-square testing and logistic regression modeling, with significance defined as P < 0.05.
Overall, the prevalence of peripheral neuropathy was 7.5%, albuminuria 10.5%, low GFR 4.1%, and both albuminuria and low GFR 2.1%. Not surprisingly, microvascular complications were more prevalent among diabetics than non-diabetics; 16.6% vs. 6.4% for neuropathy, 37.6% vs. 8.6% for albuminuria, 8.9% vs. 4.5% for low GFR, and 15.1% vs. 1.5% for both albuminuria and low GFR. Notably, the prevalence of both peripheral neuropathy and nephropathy gradually increased with rising FPG, beginning at FPG as low as 81 mg/dL. Impaired glucose tolerance and elevated FPG appear harmful even at levels previously deemed safe.
Commentary
Conclusions differ as to which factors may be important in the development of diabetic peripheral neuropathy. Height, age, disease duration, diastolic blood pressure, smoking history, low serum HDL, and high triglyceride and HbA1C were found to be significant in The European Diabetic Complications Study,1 whereas only age and duration of disease were deemed so in a later study.2 More recently, a case control study found that age, male gender, glycemic control as measured by HbA1C, and disease duration were important, whereas blood pressure, smoking, and hyperlipidemia were not.3 Hyperglycemia is unquestionably the most important modifiable risk factor, even at fasting plasma glucose levels below 126 mg/dL, and future research must be directed at addressing this issue.
References
1. Tesfaye S, Stevens LK, Stephenson JM, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: The EURODIAB IDDM Complications Study. Diabetologia 1996;39:1377-1384.
2. Ashok S, Ramu M, Deepa R, et al. Prevalence of neuropathy in type 2 diabetic patients attending a diabetes centre in South India. J Assoc Physicians India 2002;50:546-550.
3. Booya F, Bandarian F, Larijani B, et al. Potential risk factors for diabetic neuropathy: A case control study. BMC Neurology 2005;5:24doi:10.1186/1471-2377-5-24.
The risk of peripheral neuropathy gradually increases with a rise in fasting blood sugar, even at levels below that traditionally defined as diabetes mellitus.Subscribe Now for Access
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