Abstract
Background and aims Distal sensorimotor polyneuropathy (DPN) is the most common complication of diabetes. Cross-sectional studies indicate that determinants beyond hyperglycemia, such as obesity, dyslipidemia and cardiovascular disease are important, particularly in type 2 diabetes (T2DM). Methylglyoxal is a marker of oxidative stress and has been proposed as being involved in nerve fiber damage. Only few prospective studies from inception of T2DM exist. We aimed to study the development of incident DPN during the first 13 years after a screening-based diagnosis of T2DM and to identify determinants present at the time of T2DM diagnosis associated with the development of DPN.
Materials and methods From the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (the ADDITION study), 1256 participants were eligible for this prospective observational cohort study. Symptomatic DPN was assessed longitudinally by the Michigan Neuropathy Screening Instrument questionnaire (MNSI) at four time-points during follow-up. DPN was defined by a MNSI score ≥ 4. 189 participants (13%) had a positive MNSI at baseline and were thus excluded from this study. We evaluated the cumulative incidence of DPN and used Cox proportional hazard models to calculate hazard ratios (HR) to assess the association of various determinants and the development of incident DPN. Models were adjusted in steps for trial intervention group, age, sex, lipid-lowering and anti-hypertensive treatment at the 5 year follow-up of ADDITION-Denmark.
Results The median age of the study population was 60.8 years (p25;p75: 55.6;65.6), 59% were men and the median baseline HbA1c was 6.3 % (6.0;6.9) or 45.4 mmol/mol (42.1;51.9). The cumulative incidence of DPN during 13 years of follow-up was 10%. The risk of incident neuropathy was higher in older participants with a HR of 1.03 (95%CI: 1.00;1.07) per year, while sex was not associated with incident DPN with a HR of 0.67 (95% CI;0.43;1.05) for men compared to women. In Table 1 the results of Cox proportional regression models are presented. Post-hoc analyses of the association between LDL cholesterol and incident DPN demonstrated statistically significant lower levels of LDL at baseline for participants receiving lipid-lowering treatment at baseline compared to participants not receiving lipid-lowering treatment at baseline (p-value< 0.001 in a Students t-test).
Conclusion This study demonstrates a fairly low cumulative incidence of DPN defined by the MNSI in people with screen-detected T2DM. Our study provides evidence that macrovascular disease, obesity and higher levels of methylglyoxal present at the time of diagnosis of T2DM are risk factors for the development of incident DPN. The association between LDL cholesterol and incident DPN might reflect the effect of Statin treatment although this issue needs to be further elucidated.
Table 1.Risk factors for incident DPN present at the diagnosis of type 2 diabetes found by screening expressed as hazard ratios (HR) and 95% confidence intervals (CI) at two levels of adjustment.
Model A
HR (95 % CI)
Model B
HR (95 % CI)
HbA1c (%) 0.93 (0.75;1.15) 0.93 (0.75;1.15)
Systolic BP (mmHg) 1.00 (0.99;1.02) 1.00 (0.99;1.02)
Waist circumference (cm) 1.03 (1.01;1.04) * 1.03 (1.01;1.04) *
BMI (kg/m2) 1.07 (1.03;1.11) * 1.07 (1.03;1.11) *
Log albumine-creatinine ratio 1.10 (0.96;1.28) 1.12 (0.97;1.29)
Total cholesterol (mmol/L) 0.81 (0.64;1.02) 0.83 (0.66;1.04)
LDL (mmol/L) 0.70 (0.55;0.91) * 0.70 (0.55;0.91) *
HDL (mmol/L) 0.46 (0.23;0.94) * 0.46 (0.23;0.95) *
Triglycerides (mmol/L) 1.07 (0.96;1.20) 1.07 (0.97;1.18)
History of cardiovascular disease # 3.32 (1.51;7.31) * 3.22 (1.44;7.22) *
Log2 methylglyoxal (nmol/L) 1.05 (1.02;1.08) * 1.05 (1.01;1.08) *
* Indicates statistical significance with a p-value<0.05
# Non-fatal myocardial infarction or stroke in the 10-year period prior to the diagnosis of type 2 diabetes
HRs are expressed per one unit increase in each continuous risk factor and for dichotomous risk factors the unexposed group is the reference group
Model A Adjusted for intervention group, sex and age
Model B Adjusted for intervention group, sex, age, use of lipid-lowering and anti-hypertensive drugs at the 5-year follow-up
| Originalsprog | Engelsk |
|---|---|
| Publikationsdato | 1 sep. 2017 |
| Status | Udgivet - 1 sep. 2017 |
| Begivenhed | European Association for the Study of Diabetes - Portugal, Lissabon, Portugal Varighed: 11 sep. 2017 → 15 sep. 2017 |
Konference
| Konference | European Association for the Study of Diabetes |
|---|---|
| Lokation | Portugal |
| Land/Område | Portugal |
| By | Lissabon |
| Periode | 11/09/2017 → 15/09/2017 |