Increased peripheral vascular resistance as a clinical risk factor for developing diabetic nephropathy in Japanese type 2 diabetic patients

Poster Session 2

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microalbuminuric (n = 85) or albuminuric (n = 52) according to their mean albumin excretion rate, determined from two 1Zhour overnight collections. Patients with normoalbuminuria had the lowest allele frequency for Z-2 (17.6% versus 28.7% and 22.5% for microalbuminuric and albuminuric patients respectively; p
P1069 Is Microalbuminuria Associated to Other Features of Metabolic Syndrome in Japaneses? SANDRA R.G. FERREIRA, Suely G.A. Gimeno, Paul0 Rosenbaum, Laercio J. France, Magid Iunes. Preventive Medicine, Federal Universiry of Sao Paula, Sao P&o,

Sao Pa&o, Brazil

Microalbuminuria is shown to be an indicator of cardiovascular risk in some populations. The prevalence of microalbuminuria in different categories of glucose tolerance and its relationship to other cardiovascular risk factors were examined in first and second generation Japanese-Brazilians participating in an on-going population-based prevalence study of diabetes. They were submitted to clinical examination and laboratory procedures including a 75g oral GTT. This test was preceded by fasting capillary glycemia. Every subject with capillary glucose z 110 mg/dl had a early-morning urine collection for albumin determination. A sample of 2 19 individuals (109 men, 110 women) were included in the present study, being 1.5with normal glucose tolerance, 14 with impaired fasting glucose (IFG), 37 with impaired glucose tolerance (IGT) and 153 diabetics (1999 WHO criteria). Urinary albumimcreatinine ratio (ACR) were determined in urine specimens, using the DCA 2000 microalbumimcreatinine assay system. This detects albumin by an immunoturbidimetric direct antibody-antigen aggregation and measures creatinine calorimetrically using Benedict-Behre reaction. The ACR level of 17 mg/g of creatinine was considered the upper limit of normality for both sexes. The prevalence of microalbuminuria did not differ between men [33.9% (95%CI 25.1-43.6)] and women [32.7% (95%CI 24.1-42.3)] irrespective of glucose tolerance status. Diabetic people had the highest rate 139.9 (32.0-48. l)], followed by those with IGT [(24.3% (11.8-41.2)]. Only one from 14 subjects (7.1%) with IFG presented microalbuminuria and two from 15 normals (13.3%). Stratifying the groups as normo- (n=l46) and microalbuminuric one (n=73), the latter was older (59.7f10.5 vs 62.6+10.5 yrs, ~~0.03) and had higher body mass index (25.3f3.3 vs 26.5f4.3 kg/m2, ~~0.02) waist-to-hip ratio (0.87f0.06 vs 0.90*0.07, p
pure Japanese migrants population microalbuminuria is associated with other cardiovascular risk factors as demonstrated in other populations worldwide.

P1070 Pain or No Pain: What Are the Factors in Diabetic Neuropathy? LEA SORENSEN ‘,*, Rosemary McFarlane ’ , Lynda Molyneaux ‘, Dennis K. Yue I,‘. ’ Diabetes Centre, Royal Prince Alfred Hospital, Sydney, NSW; Australia; 2 Department of Medicine, University of Sydney, Sydney, NSK Australia

Why diabetic neuropathy sometimes manifests as sensory loss (insensate neuropathy) and other times as pain (painful neuropathy) is not well understood. We prospectively collected clinical information and assessed large nerve fibre function in 2472 patients with type 2 diabetes of age < 65 years. We also studied function of small nerve fibres that conduct pain sensation, in 65 patients with chronic neuropathic pain and 53 matched patients without pain. Large nerve fibre function was measured by vibration perception threshold (VPT, volts), using a biothesiometer. Small A delta nerve fibre function was measured by cold detection threshold (CDT, percentile) and C fibre function as perception of heat as pain (HPVAS, percentile). This was performed by quantitative sensory testing (QST), using a computer aided sensory evaluator (CASE IV). For the total cohort, the following factors were higher in patients with insensate neuropathy defined by a VPT z 30: duration of diabetes (+4.6 yr), age (+4.8 yr), HbAlc (+0.9%) and height (+6.0cm). Neuropathic pain was present in 11.7% of patients. Multivariate analysis confirmed these to be independent determinants (R2=0.15). Stratification into height bands showed that height rather than gender was the important factor. The only discriminants of pain were presence of insensate neuropathy (39.3%) and duration of diabetes (+4.8 yr) (R2=0.03). However, analysis of frequency distribution showed that many patients developed pain after only a short duration of diabetes. For the QST cohort, the pain group had a higher number of individuals in the worst 10 centiles of CDT (41.8% vs 34.0%). Hyperalgaesia defined as abnormally sensitive perception to heat as pain, (HPVAS in the lowest 10 centiles), was common in both patients with or without pain (59.1% vs 68.0%). In conclusion, insensate neuropathy is more common in longstanding and poorly controlled diabetes. Greater length of nerve fibre is also a significant risk factor. Although there is evidence of impaired A delta libre function in patients with pain, perception of sensation transmitted by C fibres is actually more sensitive. Development of neuropathic pain is much less predictable and not entirely explained by failure of sensory transmission due to damage of peripheral nerve fibres.

P1071 Increased Peripheral Vascular Resistance as a Clinical Risk Factor for Developing Diabetic Nephropathy in Japanese ‘Qpe 2 Diabetic Patients M. NOMURA, M. Ohashi, K. Ichida, K. Tukurimichi, J. Tanouchi, Y. Yamada, T. Kadama, H. Abe. Centerfor Diabetes Mellirus, Osaka Rosai Hospital, Osaka, Sakai, Japan We have tried to clarify the importance of vascular resistance as a clinical

risk factor for developing diabetic nephropathy in Japanese patients with type 2 (non insulin dependent diabetes mellitus) diabetes mellitus. Subjects and Methods: 179 Japanese NIDDM patients [mean ages:58f 10 years, durations:] 1f9years. Male:n=lOO, Female:n=79, mean blood pressure (BP): 133f22/72&13 mmHg] were investigated in this study. During 2 weeks hospitalization, fasting blood samples and 24-hour urine samples were taken to analyze. In order to examine peripheral vascular resistance, peripheral arterial systolic blood pressure (PASBP) at dorsalis pedis artery (DPA) and posterior tibia1 artery (PTA) were measured non-invasively with doppler blood flow analyzer. PASBP measurements were carried out

Track 2. Clinical Research

at recumbent position under stable condition by same examiner thought out the study. Results: 61 patients had diabetic nephropathy. Significantly more patients (26/57) were with nephropathy in hypertensive patients, than in the normotensive patients [35/122, p
2416 1* 11/61

RDPA

LDPA

RPTA

LPTA

(m&g)

(mm@)

(m&g)

(mmW

166f22* 121ckl4

161*19* 129zt15

175&23* 132zt12

169f23’ l3lil5

RDPA; right dorsalis pedis artery, LDPA; left dorsalis pedis artery (*: pcO.01) posterior tibial artery, LETA; left posterior tibia1 artery (meanSD)

RPTA; right

Conclusion: As clarified in this study, increased vascular resistance presented by higher peripheral arterial systolic blood pressure might be a important clinical risk factor for developing diabetic nephropathy.

P1072

Behavior of the Metabolic and Renal Function in Steadily Controlled Diabetics with Clinical Nephropathy A. ELBERT, N. Ferrari, 0. Benito, C. Berezin, A. Diaz, 0. Szyszkowsky, J. D’Alessandro, M. Ruiz. Aim: the study was designed to evaluate the evolution of diabetic nephropathy with macroproteinuria on a group of 23 patients (Group A), subjected to a 3 years continuous monitoring and good conpliance, as compared to a second group of 13 patients (Group B), who had been discontinuosly control over the same time. The study was carried out at the Diabetes and Kidney Unit, at the Hospital Clinicas, Buenos Aires, Argentina. Materials and methods: the study comprised 13 female and 23 male patients similar age (group A x 63; group B x 58 age) and of duration of diabetes (group A x 23, 13; group B x 23,36), (P < 0,90). The parameters evaluated in both groups included BMI, HbAlc, 24 hours proteinuria (P24), Creatinine Clearance (ClC), Total Cholesterol (Cal) and arterial pressure (AT). The evolution of the above parameters was assessed for the two groups at study entry and three years afterward. AT is represented by the semi-addition of the systolic and diastolic pressures. Inter and intra-group changes were assessed using the Student Test for match and unmatched pairs determinations and the “t” normal and Anova Test. Results: the BMI remained unchange throughout the 3 year study in both groups. Regarding HbAlc, the mean dropped in group A from 10,24% at study entry to 8,728 at the end, (PC 0,Ol). Group B did not show such improvement in HbAlc, (x=-9,7), (P
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P1073

Insulin, C-Peptide and Glucagon Dynamics in Chronic Renal Failure M.R. RJFAIE, A. Rasem, H. El-Soutohy, N. Gharieb, G.H. El Kanishy. Diabetes and Endocrinology University, Egypt

Unit, and Clin Path Dept., Mansoura

To explain the mechanism responsible for IGT in uremia, an intravenous glucose tolerance test (IVGTT) with 0.5 /kg glucose solution was performed on thirty patients with chronic renal failure and compared to ten, age, sex and body weight matched control. Plasma glucose(G), immunoreactive insulin (IRI), C-pcptide and Glucagon were estimated. Glucose constant decay (KG),insulin area under the curve (AUC), insulinogenic index(IGI), insulin resistance index were calculated. Uremic patients showed significantly lower values in KG, rate of insulin level decrement and significantly higher late phase insulin. However, no signilicant difference in early phase insulin level. C- peptide area under the curve was significantly increased with decreased C-peptide fraction clearence and rate of decrement.Insulin/C-peptide ratio was significantly decreased. Basal glucagon as well as glucagon area under the curve were significantly elevated. However, acute glucagon supression response(AGR) shows non significant difference. These results confirm that the common finding of IGT in chronic renal failure might be due to insulin insensivity rather than defective insulin secretion together with constant hyperglucagonemia (Both early and late phase).

P1074

Progression of Mild Diabetic Nephropathy Is Accompanied by Impaired Insulin Sensitivity and Clearance M. SVENSSON, J.W. Eriksson. Dept. of Medicine, Umeb Universiry Hospital, Sweden

Aims: Insulin action and clearance are compromised in severe renal impairment but the impact of early diabetic nephropathy is not well characterised. Methods: We studied three groups of patients with type 1 diabetes; 10 patients with no sign of nephropathy (C), 11 patients with albuminuria (albumin excretion rate, AER, 134 f153 wg/min (mea&SD), range 26-448) but normal glomerular filtration rate, GFR (A) and 8 patients with reduced GFR (58fll ml/min/1.73 m2, range 43-73) (G). Patients were matched for age, sex, BMI, diabetes duration and HbAlc. AER was measured in two overnight urine collections and GFR determined by “Cr-EDTA clearance. We utilised the euglycemic hyperinsulinemic clamp to study insulin sensitivity (M-value) and insulin clearance. Results: Patients with reduced GFR were more insulin-resistant than controls (pt0.01) and patients with albuminuria (p&03) (M-value: C 7.1f1.3 mg/kg/min, A 6.5f2.7, G 4.0f1.4). In all patients, GFR was positively correlated to the M-value (eO.52, ~~0.01). Patients with reduced GFR also had a lower insulin clearance (11.8f5.4 ml/kg/min) than patients with albuminuria (16.6f3.4, p=O.O3) and, non significantly, than controls (13.8f4.2). Among patients with reduced GFR, but not in the other two groups, there was a positive correlation between GFR and insulin clearance (1=0.71, p=O.O5). Conclusions: In patients with type 1 diabetes, albuminuria but normal GFR does not seem to alter insulin sensitivity or clearance. Progression to a stage with slightly impaired GFR appears to be accompanied by a marked insulin resistance but only a small reduction in insulin clearance. In this group of patients an increased insulin dosage may be required to maintain glycemic control.