Profile of type 2 diabetic patients referred to electroneurography laboratory/Elektronorografi laboratuvarina yonlendirilen tip 2 diyabet hastalarinin profili.
Diabetes mellitus (DM) is a complex of metabolic disorders related to insufficiency of insulin secretion, activation or both (1). Among people with diabetes, about 15% have type I and about 85% have type 2 (2). Diabetic complications are broadly divided into two groups, namely 'macrovascular'(coronary artery disease, cerebrovascular disease and peripheral vascular disease) and 'microvascular' (nephropathy, retinopathy and neuropathy) (3). Diabetic microvascular complications have severe destructive effects such as blindness, end-stage renal disease and lower extremity amputation (1).
The non-invasive laboratory examinations such as blood glucose level, A1C and urinary albumin excretion are useful in the follow-up of diabetic patients. However, careful physical and neurological examinations are still the most important. In neuropathy, symptoms and signs, such as distal symmetric numbness, pinching, and autonomic signs, are related to the type of the involved nerves. In this study, the presence of minor complications in patients with type 2 diabetes mellitus (DM) referred to electroneurography (ENG) laboratory for evaluation of neuropathy were assesed. In addition, the relationship between duration of disease, electrophysiologic findings, neurological examination findings, plasma glycated hemoglobin (A1C) levels, glucose levels and microvascular complications were examined.
Materials and Methods
Charts of four hundred and one patients with type 2 DM, referred to electrophysiology unit of our Neurology department between 2001 and 2003 years were examined. Gender, age, duration of disease, results of ophthalmological examinations (especially retinopathy-related findings), neuropathic complaints (pinching and numbness), electrophysiological examination results, neurological examination findings (deep tendon reflexes, pin-prick sensation, position senses) and laboratory examination results (blood glucose levels, A1C levels and presence of albuminuria) were all recorded retrospectively from the charts. Patients with missing data (about neurological examination findings, ophthalmological examinations and the laboratory findings) were excluded from the study. In addition, patients with vitamin B12 deficiency, intake of regular alcohol, and other endocrine problems and patients with type I DM were also excluded. Presence of other systemic diseases, such as hypertension, peripheral artery disease and stroke, were recorded in all patients.
The ENG investigation was performed with the Medelec Synergy device at a constant room temperature of 25[degrees]C using bar electrodes. Sensory responses were obtained with orthodromic methods. According to the standard polyneuropathy (PNP) examination protocol of our laboratory, motor responses of peroneal/tibial, median and ulnar nerves, sensory responses of sural, median and ulnar nerves and F wave responses were examined.
Direct and indirect ophthalmologic examination results, levels of albuminuria in 24-hour excreted urine and A1C levels were also assessed in all patients. Albuminuria was regarded as positive in patients with levels higher than 300 mg/day. The A1C levels were divided into three categories: good (A1C: 6.5%-7.5%), moderate (A1C: 7.5% above -9%) and poor (A1C: 9% above) for analyses.
All statistical analyses were performed using the SPSS for windows release 11.01 (customer number: 11494, Chicago, Ilionis). The Fisher's exact test, chi-squared, the logistic regression and ROC analyzes were used. A p value of <0.05 was taken to indicate statistical significance and the confidence interval of 95% was used.
One hundred seventy patients (102 Female/68 Male) were enrolled into the study. The mean age was 57.5 [+ or -] 11.4 years. The mean disease duration was 11.0[+ or -]7.8 years. The mean A1C level was 8.6 [+ or -] 2.2 (range 5.0-17.4), mean blood glucose level was 194.7 [+ or -] 81.
The frequency of evaluated diabetic complications in the study group is presented in Table 1. Stroke was found in 10 (5.9%) and hypertension in 94 (55%) patients. One hundred and three patients were on therapy for DM. The rates of retinopathy, albuminuria, neuropathic complaints and abnormal neurologic examination are shown in Table 2.
Forty-six patients with abnormal neurologic examination were complaining from neuropathic signs (p=0.0001, [chi square] = 20.5). While the rate of PNP was 78.2% in patients with abnormal neurologic examination, the frequency was 44.1% in the group with normal neurologic examination. This result was statistically significant (Fisher's p=0,000). The features of patients with and without PNP are shown in Table 3.
The mean duration of DM was eleven years (11.5 [+ or -] 7.8) in patients with neuropathic complaints and eight years (8.5 [+ or -] 7.6) in the ones without. There was no significant difference between genders according to neuropathic complaints (Fisher's p=0.406) and ENG abnormalities (Fisher's p=1.00). Significant correlations were found between duration of DM and retinopathy, and between ENG abnormality and neuropathic complaints (respectively: p=0.001, p=0.001, p=0.03).
The relation between three A1C groups and PNP with chi-square analysis for trend was evaluated. It was found that the frequency of PNP was increasing significantly as the A1C levels were getting poor (chi-square analysis for trend: 9.131, p=0.0051) (Table 3). PNP was detected in 34.6% of the patients with low glucose levels (under 200 mg/dl), and in 70% of the ones with high glucose (Fisher's p=0.001).
Neuropathic complaints and PNP were found to be related with the presence of retinopathy (p=0.019, [chi square] = 5.5), (p=0.000, [chi square] = 20). The rate of retinopathy was higher in patients with albuminuria (p=0.019, X2=5.5). We could not find any relationship between albuminuria and ENG abnormalities (p=0.928). Demographic features and the rate of complications of all patients are presented in Table 4.
Received of curve (ROC) analysis was made for detecting the parameters that effect development of PNP. Calculated cut off levels (with 80% specificity) for duration of DM, age and A1C levels were 7.5 years, 55.5 years and 8.7 mg/dl respectively. Logistic regression analysis to determine the relation of PNP with age, gender, A1C level and duration of DM was used. When we corrected the effect of age statistically, we found that PNP was related with gender, duration of DM and A1C levels (p<0,001). It was 3.6 fold higher in women (OR: 3.6, 95%CI: 1.5-8.8). One year increase in duration of DM caused 1.2 fold increase in the risk of PNP development (OR:1.2, 95% CI:1.1-1.3) and one point increase in the level of A1C caused 1.3 fold increase the risk of PNP development (OR:1.3, 95% CI:1.1-1.3).
It is well-known that early diagnosis and multidisciplinary approach are very important in the follow-up of diabetic patients, as microvascular complications are usually present at the time of the first diagnosis of the disease (2).
Duration of disease, presence of hyperlipidemia, hypertension, smoking, and growth factor abnormalities are found to be related with diabetic complications (1,4). Cardoso et al. reported in their study that higher mean fasting glucose level was a predictor for retinopathy and neuropathy, lower serum high-density lipoprotein cholesterol for neuropathy, and higher total cholesterol for nephropathy (5). In our study, while the frequency of PNP was 34.6% in patients with glucose level under 200mg/dl, this rate was 70% in patients with higher glucose levels. We could not evaluate the relationship between lipid profile and complications.
Distal symmetric sensorimotor PNP, entrapment neuropathies, cranial and autonomic neuropathies are the most common types of neuropathy in DM (6). Dyck et al. has reported incidence of neuropathy as 26.8% in type I and 73.2% in type 2 DM patients (7). The presence of paraesthetic and painful symptoms in history, and slowing nerve conduction velocity (NCV) in ENG studies are appear to be the earliest manifestations of PNP (1). In this study, we found that the neuropathic complaint rates were higher than those reported in the literature. This may be due to the bias in patient selection. Most of the evaluated patients in this study were the ones who were referred to our ENG laboratory because of neuropathic complaints. It is important to say that we found PNP higher in patients with abnormal neurologic examination (78.2%). There was also a significant relationship between duration of disease and neuropathic complaints, abnormal ENG findings and retinopathy.
Our results supported that A1C level is a good parameter for follow-up. One point increase in the level of A1C caused 1.3 fold increases in the risk of PNP development. Therefore, in diabetic patients, we suggest that A1C levels need to be lower than 6.5-7%, as previously reported (8).
Jawa et al. reported that the frequency of retinopathy development is 25% in the first two years of the diagnosis of DM (9). There are also other papers reporting that average time for development of retinopathy in type 2 diabetic patients is 6-7 years from the diagnosis (6,10). In our patient group, the mean disease duration was 11.0 [+ or -] 7.8 years and retinopathy was found in 34.1%. Gender, glucose and insulin levels were found to be important predictors for the onset of retinopathy (10). Sobngwi et al. reported that the rate of retinopathy was 37.5% in their series (11). They could not find any relationship between retinopathy and disease duration, however, they found that presence of microalbuminuria was related with disease duration and retinopathy. They suggested that microalbuminuria may be used as a sensitive marker for detection of early stage retinopathy (12). Villar et al. reported that hyperglycaemia and retinopathy were the most important contributors to development of incipient nephropathy in diabetic patients (13). They concluded that prevalence of proteinuria increases in accord with the severity of diabetic retinopathy. Similarly, we also found a significant relationship between retinopathy and albuminuria.
Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, hypertension and a relentless decline in glomerular filtration rate (9). Urinary microalbumin excretion is an established marker of early diabetic nephropathy and an indicator of early glomerular dysfunctions (3). Excretion of albumin less than 30-300mg/24hr or 20-200microgram/min is accepted as microalbuminuria (2,14), excretion more than 300mg/24hr is accepted as macroalbuminuria or proteinuria (15). Microalbuminuria is present in 5-10% of all patients with type 2 diabetes (16). Savage et al. concluded that urinary albumin excretion was associated with diabetic retinopathy, neuropathy and cardiovascular disease (17). In this study, we found albuminuria in thirty-three patients (19.4%). No relationship was found between disease duration and albuminuria, however, albuminuria was found to be related with the presence of retinopathy and neurologic complaints.
In summary, we found that neuropathic complaints were statistically related with the presence of retinopathy and PNP. Electrophysiological finding of PNP was related with duration of disease, abnormal neurologic examination findings, retinopathy, high levels of A1C and glucose. In general practice, taking clinical history, listening to complaints and making physical and neurological examinations are practical, and this study emphasizes that they all are quite useful in the follow-up of DM patients. Electrophysiological examinations need to be done in selected patients. In neurological outpatient clinic or multidisciplinary diabetic clinics, neurological examination including fundoscopic examination will give more details about patient's condition. We believe that ENG examination, which needs time and money, should be done in asymptomatic cases or for differential diagnosis of neuropathies with clues not related with diabetic neuropathy. Prospective studies with more patients are still needed for understanding the mechanisms that play a role in development of diabetic complications.
In conclusion, early diagnosis and prevention of complications are the goal of the treatment of diabetic patients. Development of retinopathy and nephropathy is related with neuropathy and development of these complications is related with ineffective glycemic control. ENG examination may not be routinely necessary to be performed in all diabetic patients, but is important for differential diagnosis. Detailed history, neurological and fundoscopic examinations are easy, cost-effective and reliable examinations in monitoring the development of these complications in patients with type 2 DM.
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Ufuk Emre, Aysun Unal, H. Tugrul Atasoy, Sibel Kiran *, Taner Bayraktaroglu **, Murat Sumer ***
Zonguldak Karaelmas University Faculty of Medicine, Department of Neurology, Zonguldak, Turkey
* Zonguldak Karaelmas University Faculty of Medicine, Department of Public Health, Zonguldak, Turkey
** Zonguldak Karaelmas University Faculty of Medicine, Department of General Medicine, Zonguldak, Turkey
*** MESA Hospital, Department of Neurology, Ankara, Turkey
Address for Correspondence: Ufuk Emre, MD, Zonguldak Karaelmas University Faculty of Medicine, Department of Neurology, Zonguldak, Turkey E-mail: email@example.com Received: 25.10.2009 Accepted: 21.04.2010
Table 1. Distributions of complications and other diseases Number % * Presence of neuropathic complains 141 82.9 Abnormal neurologic examination 101 59.4 ENG abnormality 140 82.4 Distal symmetric sensorimotor PNP 110 64.7 Carpal tunnel syndrome 56 32.6 Ulnar neuropathy 5 2.9 Retinopathy 58 34.1 Albuminuria 33 19.4 Hypertension (HT) 94 55 Stroke 10 5.9 * The frequency of total N (171). Table 2. Distribution of presence of polyneuropathy and A1C levels according to complications Findings * A1C With PNP (N total = 171) (mean) n (%) Diabetic retinopathy (DR) (58) 9.1 [+ or -] 1.91 51 (87.9) Abnormal neurologic examination (101) 10 [+ or -] 8.9 79 (78.2) Presence of neuropathic complains (141) 9.3 [+ or -] 7.6 99 (70.2) Presence of albuminuria (33) 8.9 [+ or -] 2 24 (72.7) Findings * Without PNP (N total = 171) n (%) Diabetic retinopathy (DR) (58) 7 (12.1) Abnormal neurologic examination (101) 22 (21.8) Presence of neuropathic complains (141) 42 (29.8) Presence of albuminuria (33) 9 (27.3) * There are one more finding belong to one patient Table 3. Features of patients with and without polyneuropathy Patents with Patents without PNP (N:110) PNP (N:61) Age (year) 61.0 [+ or -] 10. 51.0 [+ or -] 10.9 Durations of disease (year) 13.7 [+ or -] 7.6 6.0 [+ or -] 5.1 Gender Female 60.8% (62/102) 39.2% (40/102) Male 70.6% (48/68) 29.4% (20/68) Glucose 210.2 [+ or -] 82.9 166.5 [+ or -] 65.7 A1C 9.1 [+ or -] 2.2 7.8 [+ or -] 1.9 A1C Good control (1) 29.1% (32) 46.7% (28) Moderate control (2) 25.5% (28) 31.7% (19) Poor control (3) 45.5% (50) 21.7% (13) p Age (year) t: -.6.024 p = 0.000 Durations of disease (year) t: -7.791 p = 0.000 Gender Female Fisher's exact test Male p = 0.252 Glucose t: -3.761 p = 0.000 A1C t: -3.618 p = 0.000 A1C Good control (1) chi-square for Moderate control (2) trend: 9.131 Poor control (3) p = 0.0051 Table 4. Distribution of complications and findings according to features of patients Diabetic ENG retinopathy abnormality Number of patients (%) 58 (34.1%) 140 (82.4%) Duration of disease (years) * 8.7 [+ or -] 6.9 12.2 [+ or -] 7.7 Age (years) * 62.9 [+ or -] 10.3 59.7 [+ or -] 10.4 A1C (%) * 9.1 [+ or -] 1.9 9.4 [+ or -] 7.6 Gender F (%) 40 84 (39.2%) (82.4%) HT 41 (43.6%) 85 (90.4%) Stroke 7 (70%) 10 (100%) Presence of Presence of neuropathic PNP complains Number of patients (%) 110 (64.7%) 141 (82.9%) Duration of disease (years) * 13.7 [+ or -] 7.6 11.5 [+ or -] 7.7 Age (years) * 61.0 [+ or -] 10.0 58.3 [+ or -] 10.8 A1C (%) * 9.8 [+ or -] 8.6 9.3 [+ or -] 7.6 Gender F (%) 62 87 (60.8%) (85.3%) HT 69 (73.4%) 83 (88.3%) Stroke 10 (100%) 8 (80%) Abnormal Presence of neurologic albuminuria examination Number of patients (%) 33 (19.4%) 101 (59.4%) Duration of disease (years) * 12.3 [+ or -] 7.8 13 [+ or -] 7.7 Age (years) * 60.7 [+ or -] 11.9 61.7 [+ or -] 9.4 A1C (%) * 8.9 [+ or -] 2.0 10 [+ or -] 8.9 Gender F (%) 21 63 (20.6%) (61.8%) HT 21 (22.3%) 63 (67%) Stroke 2 (20%) 9 (90%) * Each value represents the mean [+ or -] S.D
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|Title Annotation:||Original Article/Orijinal Makale|
|Author:||Emre, Ufuk; Unal, Aysun; Atasoy, H. Tugrul; Kiran, Sibel; Bayraktaroglu, Taner; Sumer, Murat|
|Publication:||Turkish Journal of Endocrinology and Metabolism|
|Date:||Mar 1, 2010|
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