• 9 derivations resting electrocardiogram (ECG)
• Echocardiography
• Standard ECG stress test
• Stress Myocardial Perfusion scintigraphy if patients are not able to perform ECG stress test
• Coronary angiography if the exercise ECG stress test or stress myocardial perfusion scintigraphy suggest high probability of coronary heart disease

• Search for history of intermittent claudication
• Complete vascular examination with Ankle-Brachial Index (ABI) measurement.
• Lower limb duplex ultrasonography.

• Screening for carotid murmur at clinical examination by the same physician for all patients
• Carotid duplex ultrasonography with intima-media thickness measurement. All atherosclerotic lesions were reported.

- Renal artery duplex ultrasonography has been performed only if the patient presents a resistant hypertension treated with four drugs, including a diuretic or if blood pressure was over 180/10 mm Hg at recruitement.

• Conditions of the Ewing tests: fasting, resting at least 30mn, no hypoglycemia and no effort within 24hours, no drugs that interfere with heart rate.
• Ewing Tests for cardiac autonomic neuropathy: Beat-to-Beat heart rate variation, Heart rate response to standing, Heart rate response to valsalva maneuver, Systolic blood pressure response to standing. All tests have been performed with the same physician and aid

• History of recurrent urine tract infection and/or dysuria and/or incomplete bladder emptying
• Post voiding residual(PVR) measurement with abdominal echography by a radiologist
• Cystomanometry is performed if PVR > 50 ml
• In men the prostatic measurement was made in all patients. In women, we measured the volume of uterus.

• We interviewed all patient, looking for a history of post prandial discomfort or bad gastric emptying sensation or vomiting or unexplained diarrhea or constipation
• We performed an endoscopic examination to exclude other causes in patients with a positive history of gastro-intestinal troubles.

- Questionary: onset , drug use, medical history, psycho- social conditions

During one year of follow-up :

• We search for a recent history of intermittent claudication;
• We perform a systematic clinical examination with palpation of lower limb pulses and an Ankle-Brachial Index measurement after one year or in the presence of an acute ischemic lower limb episod ;
• Lower limb duplex sonography in the presence of an abnormal clinical vascular examination;
• Angiography in the presence of a lower limbs vascular event.

- We recorded each death and its cause from a medical record after hospitalization in emergency units or phone contact with the patient's relatives to have some news. The record began with recruitment.

Total of all reporting groups

All 327 patients had a neurological examination by the same physician to screen for Distal Diabetic Neuropathy:

• Distal sensory testing: including 10 g monofilament test, vibration perception with 128 Hz tuning fork, temperature, touch , prickling and pain perception
• Ankles and knees reflex testing
• Muscle strength testing (quadriceps and tibialis anterior)
• We use the Michigan Neuropathy Screening Instrument score. We consider the diagnosis of Distal Diabetic Neuropathy if the score is up of 2 in at least one food. The MNSI score is ranged from 0 to 5 for each food
• Use of neuropathic pain score (DN4), if the DN4 is found up or egal to 4 we consider the diagnosis of neuropathic pain. The DN4 score is ranged from 0 to 10

We exclude from analysis 10 patients (2 men and 8 women) with neuropathy because of other possible etiology (8 hypothyroidism, 1 with B12 deficiency,1 with narrowed lumbar vertebra channel)

• We screened for albuminuria or microalbuminuria in 24h urine collection with turbidimetry or immuno turbidimetry method ( performed 3 times in 4 or 6 months )
• Measurement of albumine- to- creatinine ratio (ACR), Albuminuria was diagnosed if ACR > or egal to 30 mg/g at least twice in 4 to 6 months. We ensure before performing ACR that there was no dysglycaemia, no urinary infection, no fever nor forced diuresis before we evaluate the urine sample.
• Cyto bacteriological examination and urine culture
• Serum creatinine repeated 2 to 3 time within 4 to 6 months
• Glomerular filtration rate was assessed with the Modification of Diet in Renal disease study equation (MDRD)
• Renal and urine tract echography to measure the kidneys and to screen for urine tract dilatation We made the diagnosis of Chronic Kidney Disease (CKD) if the glomerular filtration rate was < 60 ml/min/1.73 m² and/or ACR > or equal to 30 mg/g with a permanent character

Of 327 patients, 317 had a complete screening for chronic kidney disease, 5 men and 5 women were excluded from analysis because of incomplete renal status.

• Blood pressure measurement by electronic tensiometer (OMRON 3 or 4) on the right and left arm, after 10 mn of supine position.
• Three measures were performed with respect of one minute interval between each measure.
• Mean blood pressure is calculated
• Three other measures are performed in Three ulterior consultations
• Hypertension is diagnosed if the mean blood pressure >= 140 /90 mm Hg

• 9 derivations resting electrocardiogram (ECG)
• Echocardiography
• Standard ECG stress test
• Stress Myocardial Perfusion scintigraphy if patients are not able to perform ECG stress test
• Coronary angiography if the exercise ECG stress test or stress myocardial perfusion scintigraphy suggest high probability of coronary heart disease

88.9 % (291 patients) had a screening for coronary heart disease. We performed an electrocardiogram in 325 cases, an echocardiography in 317 cases, a myocardial ischemic test in 291 cases (223 for silent myocardial ischemia: 85 men and 138 women) and a coronarography in 18 cases ( 8 men and 10 women, all had a positive myocardial ischemic test)

• Search for history of intermittent claudication
• Complete vascular examination with Ankle-Brachial Index (ABI) measurement.
• Lower limb duplex ultrasonography.

Lower limb duplex ultrasonography measurement has been done in 306 among 327 patients (111 men and 195 women). 21 patients, with a lack of data,were excluded from analysis. Chi 2 test was used for comparison of proportions.

• Screening for carotid murmur at clinical examination by the same physician for all patients
• Carotid duplex ultrasonography with intima-media thickness measurement. All atherosclerotic lesions were reported.

From 327, 304 patients (109 men and 195 women) could perfom duplex ultrasonography of supra aortic trunks. We focus on the examination of external and internal carotids.

- Renal artery duplex ultrasonography has been performed only if the patient presents a resistant hypertension treated with four drugs, including a diuretic or if blood pressure was over 180/10 mm Hg at recruitement.

From 327 we perform a duplex ultrasonography of renal arteries in 16 patients (6 men and 10 women) The number of participants analyzed is too small to have a statistical analysis.

• Conditions of the Ewing tests: fasting, resting at least 30mn, no hypoglycemia and no effort within 24hours, no drugs that interfere with heart rate.
• Ewing Tests for cardiac autonomic neuropathy: Beat-to-Beat heart rate variation, Heart rate response to standing, Heart rate response to valsalva maneuver, Systolic blood pressure response to standing. All tests have been performed with the same physician and aid

We screened 283 patients from 327 (100 men and 183 women). We excluded 44 patients from analysis (22 men and 22 women)cause of beta blocker treatment or high blood pressure, or diabetic retinopathy, or severe coronary heart disease and patients that could not perform deep breathing.

• History of recurrent urine tract infection and/or dysuria and/or incomplete bladder emptying
• Post voiding residual(PVR) measurement with abdominal echography by a radiologist
• Cystomanometry is performed if PVR > 50 ml
• In men the prostatic measurement was made in all patients. In women, we measured the volume of uterus.

From 327 we could screen 318 patients (118 men and 200 women) for bladder autonomic neuropathy. We performed a cystomanometry in 4 patients. We exclude, from analysis, 9 patients who didn't come to perform the post-voiding volume measurement.

• We interviewed all patient, looking for a history of post prandial discomfort or bad gastric emptying sensation or vomiting or unexplained diarrhea or constipation
• We performed an endoscopic examination to exclude other causes in patients with a positive history of gastro-intestinal troubles.

An endoscopic examination has been performed in six women whose report vomiting, nausea or constipation. In the men's group no-one had an endoscopic examination.

- Questionary: onset , drug use, medical history, psycho- social conditions

• We Record every documented acute coronary syndrome during follow-up;
• Each patient had an electrocardiogram every 3 months and during acute cardiovascular events;
• Echocardiography has been performed if indicated by the cardiologist.

305 patients (112 men and 193 women) were re-evaluated one year after recruitment. From 327 patients enrolled, we excluded 22 patients (10 men and 12 women) from the analysis because of a lack of data, they were lost from follow-up. We include in analysis 5 patients who died the three first months during follow-up.

• We assessed every new clinical signs of stroke with an interview searching for acute neurological symptoms and a clinical examination for all patients, from day one of recruitment to one year of follow-up;
• Tomodensitometry if there was a clinical presentation of stroke. Magnetic resonance imaging if transient ischemic attack was suspected.

300 patients (109 men and 191 women) were re-evaluated one year after recruitment. From 327 patients enrolled, we excluded 27 patients (13 men and 14 women) from the analysis because of a lack of data. 22 patients (10 men and 12 women) were lost from follow-up and 5 died too early during follow-up (three first months).

During one year of follow-up :

• We search for a recent history of intermittent claudication;
• We perform a systematic clinical examination with palpation of lower limb pulses and an Ankle-Brachial Index measurement after one year or in the presence of an acute ischemic lower limb episod ;
• Lower limb duplex sonography in the presence of an abnormal clinical vascular examination;
• Angiography in the presence of a lower limbs vascular event.

300 patients (109 men and 191 women) were re-evaluated one year after recruitment. From 327 patients enrolled, we excluded 27 patients (13 men and 14 women) from the analysis because of a lack of data, 22 patients (10 men and 12 women) were lost from follow-up and 5 died too early during follow-up (three first months).

- We recorded each death and its cause from a medical record after hospitalization in emergency units or phone contact with the patient's relatives to have some news. The record began with recruitment.

From 327 patients (122 men and 205 women) enrolled, 305 were followed-up one year or until death (112 men and 193 women). 22 patients (10 men and 12 women) were excluded from analysis because lost during follow-up.

From 205 women, 193 had been followed-up one year or until death. 191 women had complete one year of follow-up.