Short-term changes after a weight reduction intervention in advanced diabetic nephropathy.
OBJECTIVE
Obesity precedes and is strongly linked to the development of type 2 diabetic nephropathy in most patients, yet little is known about the effects of weight reduction on this disease. This study aimed to establish proof of concept for the hypothesis that weight reduction ameliorates diabetic nephropathy.


METHODS
Six obese individuals with advanced diabetic nephropathy (estimated GFR <40 ml/min per 1.73 m(2), urine albumin excretion >30 mg/d) currently taking a renin-aldosterone axis inhibitor underwent a 12-week very low calorie ketogenic weight reduction diet with encouragement of exercise between March and September 2012. Albuminuria and other parameters of kidney health were the main outcome measures.


RESULTS
There was a 12% reduction in weight (median 118.5 versus 104.3 kg, P=0.03). The intervention was associated with a 36% reduction in albuminuria that did not reach statistical significance (2124 versus 1366 mg/24 h, P=0.08) and significant reductions in the filtration markers serum creatinine (3.54 versus 3.13 mg/dl, P<0.05) and cystatin C (2.79 versus 2.46 mg/l, P<0.05). Improvements were also noted for the diabetes markers fasting glucose (166 versus 131 mg/dl, P<0.05), fasting insulin (26.9 versus 10.4 μU/ml, P<0.05), and insulin resistance (9.6 versus 4.2, P=0.03). Physical function, general health, and the number of diabetes medications also showed statistically significant signs of improvement.


CONCLUSIONS
After a short-term intensive weight reduction intervention in patients with advanced diabetic nephropathy, improvements were observed in markers of glomerular filtration, diabetes status, and risk factors for kidney disease progression, as well as other general indicators of health and well-being.
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana;, †Department of Environmental Health, Indiana University, Bloomington, Indiana, ‡Department of Medicine, Fayette Regional Health System, Connersville, Indiana.
Allon N
AN
Friedman
Mary
M
Chambers
Lisa M
LM
Kamendulis
Joan
J
Temmerman
D000368:Aged; D000419:Albuminuria / Q000209:etiology / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D055423:Diet, Ketogenic; D018450:Disease Progression; D005081:Exercise Therapy; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007196:Indiana; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D010865:Pilot Projects; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015431:Weight Loss
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D003404:Creatinine