Microalbuminuria Associated With Diabetic Neuropathy

Bell, David S.H.; Ketchum, C H; Robinson, C A; Wagenknecht, Lynne E.; Williams, B. T.

doi:10.2337/diacare.15.4.528

Cited by 29 publications

(17 citation statements)

References 20 publications

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“…Our study groups were carefully characterized and because of potential links with AN they were matched for age, gender, diabetes duration, and smoking status [16,17]. In keeping with the results of previous studies [18][19][20][21][22], microalbuminuric and normoalbuminuric groups showed differences in some clinical variables (Table 2). Our comparison of autonomic function in MA and NA groups excludes, through careful matching, the effects of age, gender, diabetes duration, and smoking status but there are various reasons why differences in autonomic function might not be explained only by differences in AER.…”

Section: Discussionmentioning

confidence: 89%

Autonomic neuropathy in asymptomatic subjects with non-insulin-dependent diabetes mellitus and microalbuminuria

Rutter

McComb

Brady

et al. 1998

Clinical Autonomic Research

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Patients with non-insulin-dependent diabetes mellitus (NIDDM) and microalbuminuria (MA) are at increased risk of early death. In NIDDM patients without evidence of heart disease, we examined the links between MA and autonomic neuropathy (AN) and reduced heart rate variability (HRV), both of which have been linked to a poor prognosis. We have studied 43 asymptomatic NIDDM patients with MA and have matched them with 43 normoalbuminuric patients for age, gender, diabetes duration, and smoking status. AN was assessed by heart rate changes to deep breathing, Valsalva, and posture and blood pressure changes to posture and hand grip. Twenty-four hour Holter monitoring was used to evaluate HRV. Patients with MA showed evidence of AN and reduced HRV when compared with normoalbuminuric patients. In multivariate analysis, with measures of AN and HRV as outcome variables, Log albumin excretion rate was a significant independent predictor but stronger predictors were the presence of diabetic retinopathy, age, body mass index, claudication, alcohol consumption, and calcium channel blocker use. The presence of MA is linked to AN and reduced HRV in asymptomatic NIDDM patients. The nature of the relationship is complex, involving multiple relationships with other clinical parameters.

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Section: Discussionmentioning

confidence: 89%

Autonomic neuropathy in asymptomatic subjects with non-insulin-dependent diabetes mellitus and microalbuminuria

Rutter

McComb

Brady

et al. 1998

Clinical Autonomic Research

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“…The association of albuminuria with the presence of neuropathy has been demonstrated in a number of studies involving IDDM subjects [48,49], but this is the first demonstration in patients with NIDDM. Although the exact pathogenesis of diabetic neuropathy is still under question, morphological studies suggest that an ischaemic aetiology is involved in the pathogenesis of diabetic polyneuropathy [50].…”

Section: Discussionmentioning

confidence: 97%

Appropriate Blood Pressure Control in NIDDM (ABCD) Trial

1996

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There is considerable epidemiologic evidence suggesting that hypertension plays a significant role in the development and progression of diabetic nephropathy [1], retinopathy [2,3], cardiovascular disease [4][5][6][7], and neuropathy [8] in patients with non-insulindependent diabetes mellitus (NIDDM). Furthermore, several studies have demonstrated a significant increase in mortality in diabetic patients with hypertension [9,10]. Although the epidemiological evidence demonstrating the strong association between hypertension and diabetic vascular complications is compelling, no intervention studies have been done to evaluate the efficacy of antihypertensive therapy in preventing these complications in patients with NIDDM. The absence of intervention studies in the NIDDM population is particularly remarkable, since NIDDM patients account for more than 90 % of all diabetic patients [11] and 60 % of diabetic end-stage renal disease in the United States. Moreover, endstage renal disease secondary to diabetes costs the Diabetologia (1996)

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“…Another limitation of this study is that it did not evaluate the effects of these drug–drug interactions in the target patient population. Diabetes is frequently complicated by renal and hepatic impairment 18, 19. Since the metabolism and clearance of drugs may be different in patients with renal and hepatic impairment, future studies are needed to evaluate the PK and safety of mirogabalin coadministered with probenecid or cimetidine in these patients.…”

Section: Discussionmentioning

confidence: 99%

Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open‐label, drug–drug interaction study

Tachibana

Yamamura

Atiee

et al. 2018

Brit J Clinical Pharma

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AimsThe primary aim of this study was to assess the individual effects of probenecid and cimetidine on mirogabalin exposure.MethodsThis phase 1, open‐label, crossover study randomized healthy adults to receive three treatment regimens, each separated by ≥5‐day washout: a single oral dose of mirogabalin 15 mg on day 2, mirogabalin 15 mg on day 2 plus probenecid 500 mg every 6 h from days 1 to 4, and mirogabalin 15 mg on day 2 plus cimetidine 400 mg every 6 h from days 1 to 4.ResultsCoadministration of mirogabalin with probenecid or cimetidine increased the maximum and total mirogabalin exposure. The geometric mean ratios of Cmax and AUC(0‐t) (90% CI) with and without coadministration of probenecid were 128.7% (121.9–135.7%) and 176.1% (171.9–180.3%), respectively. The geometric mean ratios of Cmax and AUC(0‐t) (90% CI) with and without coadministration of cimetidine were 117.1% (111.0–123.6%) and 143.7% (140.3–147.2%), respectively. Mean (standard deviation) renal clearance of mirogabalin (l h–1) was substantially slower after probenecid [6.67 (1.53)] or cimetidine [7.17 (1.68)] coadministration, compared with mirogabalin alone [11.3 (2.39)]. Coadministration of probenecid or cimetidine decreased mirogabalin mean (standard deviation) apparent total body clearance [10.5 (2.33) and 12.8 (2.67) l h–1, respectively, vs. 18.4 (3.93) for mirogabalin alone].ConclusionsA greater magnitude of change in mirogabalin exposure was observed when coadministered with a drug that inhibits both renal and metabolic clearance (probenecid) vs. a drug that only affects renal clearance (cimetidine). However, as the increase in exposure is not clinically significant (>2‐fold), no a priori dose adjustment is recommended.

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Microalbuminuria Associated With Diabetic Neuropathy

Abstract: Microalbuminuria is independently associated with diabetic neuropathy. This association lends support to the theory of a vascular etiology for diabetic distal symmetrical neuropathy.

Cited by 29 publications

References 20 publications

Autonomic neuropathy in asymptomatic subjects with non-insulin-dependent diabetes mellitus and microalbuminuria

Autonomic neuropathy in asymptomatic subjects with non-insulin-dependent diabetes mellitus and microalbuminuria

Appropriate Blood Pressure Control in NIDDM (ABCD) Trial

Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open‐label, drug–drug interaction study

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