Kidney function in newly diagnosed Type 2 (non-insulin-dependent) diabetic patients, before and during treatment

Schmitz, A.; Hansen, Henning Otte; Christensen, T.

doi:10.1007/bf00271263

Cited by 69 publications

(44 citation statements)

References 32 publications

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“…In IDDM each ofthese abnormalities has been more marked in the presence of uncontrolled hyperglycemia (4,5) and moderated by insulin treatment into a range similar to that observed in the modestly hyperglycemic subjects ofthe present study (6,18,29). Although measurable hyperfiltration could not be clearly demonstrated in an older population with NIDDM of recent onset, insulin treatment also resulted in a significant depression of GFR under these circumstances (30). Thus, the prevailing GFR appears to be related to the level of glycemia, both in insulin-and noninsulin-dependent diabetes mellitus.…”

Section: Discussionsupporting

confidence: 72%

Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

Myers

Nelson²,

Williams³

et al. 1991

J. Clin. Invest.

129

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Differential solute clearances were used to characterize glomerular function in 20 Pima Indians with noninsulin-dependent diabetes mellitus (NIDDM) of < 3 yr duration. 28 Pima Indians with normal glucose tolerance served as controls. In the diabetic group, the glomerular filtration rate (GFR, iothalamate clearance) exceeded the control value by 15% (140±6 vs. 122±5 ml/min, P < 0.01). A corresponding 12% increase in renal plasma flow (RPF) was not statistically significant and did not account fully for the observed hyperfiltration, suggesting a concomitant elevation of the ultrafiltration pressure or coefficient. The median albumin excretion ratio in NIDDM exceeded control by almost twofold (10.1 vs. 5.8 mg/g creatinine), a trend which just failed to achieve statistical significance (P = 0.06). Fractional clearances of dextrans of broad size distribution were also elevated in diabetic subjects, significantly so for larger dextrans of between 48 and 60 A radius. A theoretical analysis of dextran transport through a heteroporous membrane revealed glomerular pores in NIDDM to be uniformly shifted towards pores of larger size than in controls. We conclude that an impairment of barrier size selectivity combined with high GFR elevates the filtered protein load in NIDDM of recent onset. We propose that enhanced transglomerular trafficking of protein may predispose to sclerosis of glomeruli in those Pima Indians with NIDDM who ultimately develop diabetic nephropathy. (J. Clin. Invest. 1991. 88:524-530.) Key words: hyperfiltration * barrier size-selectivity * transmembrane protein shunting. heteroporous membrane models Introduction Considerable evidence in experimental animals and some indirect evidence in humans suggests that the development ofinsu-

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Section: Discussionsupporting

confidence: 72%

Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

Myers

Nelson²,

Williams³

et al. 1991

J. Clin. Invest.

129

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“…The high rates of hyperfiltration in new-onset diabetes may be explained, at least partly, by the acute metabolic effect of hyperglycaemia, as previous studies have demonstrated an association between hyperglycaemia and hyperfiltration as well as nephromegaly [23,24]. Improved glycaemic control has been shown to reduce GFR and kidney size [25,26] Long-term hyperglycaemia has also been correlated with elevated GFR in type 1 diabetes [27]. In contrast, we did not find any difference in glycaemic control between the age-unadjusted and -adjusted hyperfiltration and control groups.…”

Section: Discussionmentioning

confidence: 97%

Renal hyperfiltration in type 2 diabetes: effect of age-related decline in glomerular filtration rate

et al. 2005

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Aims/hypothesis: We sought to characterise the effect of the age-related decline of GFR on hyperfiltration in type 2 diabetes and to identify clinical characteristics associated with hyperfiltration. Materials and methods: GFR was measured in 662 type 2 diabetic patients by plasma disappearance of 99 m-technetium-diethylene-triaminepenta-acetic acid. The prevalence of hyperfiltration was calculated using both an age-unadjusted GFR threshold of >130 ml min −1 1.73 m −2 and an age-adjusted threshold incorporating a decline of 1 ml min −1 year −1 after the age of 40. The hyperfiltering patients were compared with type 2 diabetic subjects who had a GFR between 90 and 130 ml min −1 1.73 m −2 and were matched for age, sex and disease duration to allow for identification of modifiable factors associated with hyperfiltration. Results: The prevalence of hyperfiltration was 7.4% when age-unadjusted and 16.6% when age-adjusted definitions were used. The age-unadjusted vs -adjusted prevalence rates for hyperfiltration were 50 vs 50%, 12.9 vs 23.4% and 0.3 vs 9.0% for patients aged <40 years, 40 to 65 years and >65 years, respectively. Both the age-unadjusted and -adjusted hyperfiltration groups had lower mean diastolic blood pressure and lower serum creatinine levels than the control groups. Although the ageunadjusted hyperfiltration group had larger kidneys compared to the control group, this difference was no longer significant when the age-adjusted definition was used. There were no differences in HbA 1 c, mean arterial pressure, antihypertensive use, insulin therapy, dyslipidaemia, frequency of macro-or microvascular complications, BMI, urinary sodium, urea and albumin excretion between the groups. Conclusions/interpretation: Hyperfiltration was still more common among younger patients with type 2 diabetes even after adjusting for the expected age-related decline in GFR. Hyperfiltration was associated with a lower mean diastolic blood pressure independent of age.

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“…Gilbert et al [30] reported a significant association between rate of change in UAE and HbAlc in progressors, but whether this was due to those with poor control having a higher average is unclear. Optimising glycaemic control reduces albuminuria at least in shortterm studies [12,[15][16], but the long-term consequences of such intervention are unknown in NIDDM patients.…”

Section: Discussionmentioning

confidence: 99%

“…Persistent microalbuminuria (i. e. a urinary albumin excretion (UAE) from 20 ~g/min to 200 ~g/min) in patients with IDDM defines the state of incipient nephropathy [3], which is the state from which approximately 80 % progress to overt nephropathy over the next decade. Microalbuminuria [4,[6][7][8][9][10][11], and often present at diagnosis or at early known durations [4,[11][12][13][14][15][16]. Microalbuminuria in NIDDM obviously do also predict the development of clinical proteinuria [17], which will progress in some cases to renal failure, but with far less consistency than is seen in IDDM [18].…”

mentioning

confidence: 99%

Systolic blood pressure relates to the rate of progression of albuminuria in NIDDM

1994

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SummaryWe prospectively followed a cohort of 278 non-insulin-dependent (NIDDM) patients for a 6-year period, intending to estimate the rate of increase of albuminuria and to identify clinical variables that influence this increase. At baseline, normoalbuminuria (N) was seen in 74 %, microalbuminuria (M) in 19 % and 7 % presented with proteinuria (P). A total of 80patients died; they were older (p < 0.001) and had higher albumin excretion both at baseline and as an average during follow-up (p < 0.01). At baseline, patients with proteinuria had higher blood pressures (systolic and diastolic), whereas there was no difference between patients with normo-and microalbuminuria. Glycaemic control was increasingly poor throughout the three groups. At follow-up, an average relative rate of increase of albuminuria (slope) of 17 % per year was seen both for patients with complete 6 years, follow-up (n = 135) and patients with at least 4 years follow-up (n = 178). Slope correlated significantly with systolic blood pressure (r = 0.26 and 0.29) in both groups, diastolic blood pressure only in the 4-year group (r = 0.22) and average albuminuria in both (r = 0.31 and 0.24). By multiple regression analyses systolic blood pressure and average albuminuria remained with significant influence on slope. Progression was defined as an increase in the category (e. g. normoto microalbuminuria) as well as an increase of more than 20 % in albumin excretion, and was seen in 46 patients with at least 4 years' follow-up. Progressors (patients demonstrating progression) had higher systolic blood pressure (165 mmHg + 20 vs 156 + 17) and poorer glycaemic control (HbAm: 8.2 % + 1.5 vs 7.7 + 1.3) p < 0.05, as well as a higher level of albuminuria at baseline. The present study points to systolic blood pressure and general level of albuminuria as factors determining the rate of progression of albuminuria. However, only a modest fraction of the variation between subjects was explained by these variables. [Diabetologia (1994[Diabetologia ( ) 37: 1251[Diabetologia ( -1258 Key words Non-insulin-dependent diabetes mellitus, albuminuria, blood pressure, rate of progression, progressors, glycaemic control. Abbreviations: IDDM, insulin-dependent diabetes mellitus; NIDDM, non-insulin-dependent diabetes mellitus; N, normal urinary albumin excretion; M, microalbuminuria; R proteinuria; Slope, relative rate of increase; UAC, urinary albumin concentration; UAE, urinary albumin excretion rate.The natural development of diabetic nephropathy pertaining to patients with non-insulin-dependent diabetes (NIDDM) is poorly elucidated [1,2]. In insulin-dependent diabetes (IDDM) approximately 30 % of patients eventually develop end-stage renal failure [3], whereas in NIDDM the proportion is much lower (less than 10 %) at least in elderly Caucasian populations [4][5][6][7]. Persistent microalbuminuria (i. e. a urinary albumin excretion (UAE) from 20 ~g/min to 200 ~g/min) in patients with IDDM defines the state of incipient nephropathy [3], which is the state from which appr...

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Kidney function in newly diagnosed Type 2 (non-insulin-dependent) diabetic patients, before and during treatment

Cited by 69 publications

References 32 publications

Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

Renal hyperfiltration in type 2 diabetes: effect of age-related decline in glomerular filtration rate

Systolic blood pressure relates to the rate of progression of albuminuria in NIDDM

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