Subscribe to RSS
DOI: 10.1055/s-0031-1271622
© Georg Thieme Verlag KG Stuttgart · New York
Change in the Amount of Body Fat and IL-6 Levels is Related to Altered Insulin Sensitivity in Type 1 Diabetes Patients with or without Diabetic Nephropathy
Publication History
received 05.07.2010
accepted 20.12.2010
Publication Date:
14 February 2011 (online)

Abstract
Insulin resistance (IR) is found early-on in renal disease. The aim of this study was to prospectively evaluate if a change in glomerular filtration rate (GFR) or in endocrine and inflammatory factors over time alters insulin sensitivity in patients with type 1 diabetes (T1D) or without diabetic nephropathy (DN) at baseline. 20 T1D with (DN+, n=12) or without DN (DN–, n=8) were re-examined after 5.0±0.4 years. GFR was determined by 51Cr-EDTA clearance. Insulin sensitivity was assessed by hyperinsulinemic (56 mU/m2/min), euglycemic clamp (M-value at steady state during clamp) and calculated per lean body mass. Body composition was determined by bioimpedance. No association was found between change in GFR and change in M-value over time. Instead, change in M-value was associated to change in fat mass (%) and change in IL-6 levels in all subjects taken together (r=−0.55, p=0.012 and r=−0.62, p=0.006). These association were verified in the multivariate regression analyses. Findings were similar in DN − and DN +, respectively, but the change in IL-6 was only significantly associated with altered M-value in DN+ subjects. This prospective study indicates that change in amount body fat and levels of inflammatory cytokines, such as IL-6, contribute to change in insulin resistance over time in type 1 diabetes patients with and without diabetic nephropathy.
Key words
type 1 diabetes - diabetic nephropathy - glucose metabolism - insulin sensitivity - hormones - cytokines
References
- 1
Mogensen CE, Christensen CK, Vittinghus E.
The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic
nephropathy.
Diabetes.
1983;
32
(S 02)
64-78
MissingFormLabel
- 2
Yip J, Mattock MB, Morocutti A, Sethi M, Trevisan R, Viberti G.
Insulin resistance in insulin-dependent diabetic patients with microalbuminuria.
Lancet.
1993;
342
883-887
MissingFormLabel
- 3
Yudkin JS, Forrest RD, Jackson CA.
Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington
Diabetes Survey.
Lancet.
1988;
2
530-533
MissingFormLabel
- 4
Mykkanen L, Zaccaro DJ, Wagenknecht LE, Robbins DC, Gabriel M, Haffner SM.
Microalbuminuria is associated with insulin resistance in nondiabetic subjects: the
insulin resistance atherosclerosis study.
Diabetes.
1998;
47
793-800
MissingFormLabel
- 5
DeFronzo RA, Alvestrand A.
Glucose intolerance in uremia: site and mechanism.
Am J Clin Nutr.
1980;
33
1438-1445
MissingFormLabel
- 6
DeFronzo RA, Alvestrand A, Smith D, Hendler R, Hendler E, Wahren J.
Insulin resistance in uremia.
J Clin Invest.
1981;
67
563-568
MissingFormLabel
- 7
Eidemak I, Feldt-Rasmussen B, Kanstrup IL, Nielsen SL, Schmitz O, Strandgaard S.
Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal
failure and its association with aerobic work capacity.
Diabetologia.
1995;
38
565-572
MissingFormLabel
- 8
Fliser D, Pacini G, Engelleiter R, Kautzky-Willer A, Prager R, Franek E, Ritz E.
Insulin resistance and hyperinsulinemia are already present in patients with incipient
renal disease.
Kidney Int.
1998;
53
1343-1347
MissingFormLabel
- 9
Svensson M, Yu ZW, Eriksson JW.
A small reduction in glomerular filtration is accompanied by insulin resistance in
type I diabetes patients with diabetic nephrophathy.
Eur J Clin Invest.
2002;
32
100-109
MissingFormLabel
- 10
Becker B, Kronenberg F, Kielstein JT, Haller H, Morath C, Ritz E, Fliser D.
Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients
with kidney disease: the mild and moderate kidney disease study.
J Am Soc Nephrol.
2005;
16
1091-1098
MissingFormLabel
- 11
Svensson M, Eriksson JW.
Insulin resistance in diabetic nephropathy – cause or consequence?.
Diabetes Metab Res Rev.
2006;
22
401-410
MissingFormLabel
- 12
Cooper-DeHoff RM, Pacanowski MA, Pepine CJ.
Cardiovascular therapies and associated glucose homeostasis: implications across the
dysglycemia continuum.
J Am Coll Cardiol.
2009;
53
S28-S34
MissingFormLabel
- 13
Goicoechea M, de Vinuesa SG, Lahera V, Cachofeiro V, Gomez-Campdera F, Vega A, Abad S, Luno J.
Effects of atorvastatin on inflammatory and fibrinolytic parameters in patients with
chronic kidney disease.
J Am Soc Nephrol.
2006;
17
S231-S235
MissingFormLabel
- 14
Biesenbach G, Raml A, Schmekal B, Eichbauer-Sturm G.
Decreased insulin requirement in relation to GFR in nephropathic Type 1 and insulin-treated
Type 2 diabetic patients.
Diabet Med.
2003;
20
642-645
MissingFormLabel
- 15
Svensson M, Eriksson JW.
No direct link between albumin excretion rate and insulin resistance – a study in
type 1 diabetes patients with mild nephropathy.
Horm Metab Res.
2002;
34
254-259
MissingFormLabel
- 16
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Diabetes Care.
1997;
20
1183-1197
MissingFormLabel
- 17
Granerus G, Aurell M.
Reference values for 51Cr-EDTA clearance as a measure of glomerular filtration rate.
Scand J Clin Lab Invest.
1981;
41
611-616
MissingFormLabel
- 18
DeFronzo RA, Tobin JD, Andres R.
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
Am J Physiol.
1979;
237
E214-E223
MissingFormLabel
- 19
DeFronzo RA, Ferrannini E, Sato Y, Felig P, Wahren J.
Synergistic interaction between exercise and insulin on peripheral glucose uptake.
J Clin Invest.
1981;
68
1468-1474
MissingFormLabel
- 20
Bokemark L, Froden A, Attvall S, Wikstrand J, Fagerberg B.
The euglycemic hyperinsulinemic clamp examination: variability and reproducibility.
Scand J Clin Lab Invest.
2000;
60
27-36
MissingFormLabel
- 21
Eriksson JW, Jansson PA, Foley K, Lithell H.
Insulin sensitivity following treatment with the alpha 1-blocker bunazosin retard
and the beta 1-blocker atenolol in hypertensive non-insulin-dependent diabetes mellitus
patients.
J Hypertens.
1996;
14
1469-1475
MissingFormLabel
- 22
Ahmad J, Siddiqui MA, Ahmad H.
Effective postponement of diabetic nephropathy with enalapril in normotensive type
2 diabetic patients with microalbuminuria.
Diabetes Care.
1997;
20
1576-1581
MissingFormLabel
- 23
Lender D, Arauz-Pacheco C, Adams-Huet B, Raskin P.
Essential hypertension is associated with decreased insulin clearance and insulin
resistance.
Hypertension.
1997;
29
111-114
MissingFormLabel
- 24
Ferrannini E, Wahren J, Faber OK, Felig P, Binder C, DeFronzo RA.
Splanchnic and renal metabolism of insulin in human subjects: a dose-response study.
Am J Physiol.
1983;
244
E517-E527
MissingFormLabel
- 25
Lukaski HC, Bolonchuk WW, Hall CB, Siders WA.
Validation of tetrapolar bioelectrical impedance method to assess human body composition.
J Appl Physiol.
1986;
60
1327-1332
MissingFormLabel
- 26
Vareesangthip K, Tong P, Wilkinson R, Thomas TH.
Insulin resistance in adult polycystic kidney disease.
Kidney Int.
1997;
52
503-508
MissingFormLabel
- 27
Nerpin E, Riserus U, Ingelsson E, Sundstrom J, Jobs M, Larsson A, Basu S, Arnlov J.
Insulin sensitivity measured with euglycemic clamp is independently associated with
glomerular filtration rate in a community-based cohort.
Diabetes Care.
2008;
31
1550-1555
MissingFormLabel
- 28
Robertson L, Waugh N, Robertson A.
Protein restriction for diabetic renal disease.
Cochrane Database Syst Rev.
2007;
CD002181
MissingFormLabel
- 29
Trirogoff ML, Shintani A, Himmelfarb J, Ikizler TA.
Body mass index and fat mass are the primary correlates of insulin resistance in nondiabetic
stage 3–4 chronic kidney disease patients.
Am J Clin Nutr.
2007;
86
1642-1648
MissingFormLabel
- 30
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM.
Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity
and insulin resistance.
J Clin Invest.
1995;
95
2409-2415
MissingFormLabel
- 31
Natali A, Toschi E, Baldeweg S, Ciociaro D, Favilla S, Sacca L, Ferrannini E.
Clustering of insulin resistance with vascular dysfunction and low-grade inflammation
in type 2 diabetes.
Diabetes.
2006;
55
1133-1140
MissingFormLabel
- 32
Cartier A, Lemieux I, Almeras N, Tremblay A, Bergeron J, Despres JP.
Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6
and tumor necrosis factor-alpha in men.
J Clin Endocrinol Metab.
2008;
93
1931-1938
MissingFormLabel
- 33
Astrup AS, Tarnow L, Pietraszek L, Schalkwijk CG, Stehouwer CD, Parving HH, Rossing P.
Markers of endothelial dysfunction and inflammation in type 1 diabetic patients with
or without diabetic nephropathy followed for 10 years: association with mortality
and decline of glomerular filtration rate.
Diabetes Care.
2008;
31
1170-1176
MissingFormLabel
Correspondence
Dr. M. Svensson
Department of Nephrology
Sahlgrenska University Hospital
41345 Gothenburg
Sweden
Phone: +46/761/301 133
Fax: +46/31/824 660
Email: maria.svensson@wlab.gu.se