A 73-year-old male diabetic of Caucasian ethnicity presented with progressive weakness and vertigo for one week at the Neurology Department of the University Hospital Halle. He had a background history of diabetic polyneuropathy, and clinical examination showed decreased muscle reflexes and hypopallesthesia. The patient depended on a wheelchair for 4 years before hospitalization. However, he still managed to walk distances of up to 10 m using a walking aid. Electrophysiological investigation showed a sensorimotor axonal and demyelinating peripheral neuropathy. As concomitant diseases, substituted hypothyroidism and metabolic syndrome with obesity (weight: 105 kg, height: 184 cm, body-mass index: 31.0 kg/m²), dyslipidemia, arterial hypertension and type-2 diabetes for more than 20 years were known. Four years before hospitalization, a unilateral knee and hip-replacement surgeries were performed. Due to uncontrolled arterial hypertension, urapidil (60 mg thrice a day) was added, before hospitalization, to his known antihypertensive medications with valsartan (160 mg BID) and bisoprolol (5mg BID). At admission, arterial hypertension still was uncontrolled, HbA1c was 11.2%, the kidney function was not impaired. Diabetes therapy consisted of fixed-dose prandial insulin (Actrapid®, 40 units thrice a day) and basal insulin analog (insulin glargine, 40 units QD) with a daily cumulative insulin dose of 160 units. Documented or symptomatic hypoglycemic episodes were not reported by the patient. Intermittent blood-glucose test results during the hospital stay and routine laboratory results at admission are summarized in Tables 1 and 2. The patient was admitted to an Intermediate-Care Unit initially, due to hyperglycemia, based on intermittent blood glucose, and hypertensive crisis. The insulin therapy was switched to intensive conventional therapy resulting in a cumulative insulin dose of 46 units per day after 11 days in the hospital. In addition, metformin (500 mg QD), empagliflozin (10 mg QD), a sodium-glucose transporter-2 inhibitor (SGLT-2i), and dulaglutide (1.5 mg per week), a subcutaneously applied glucagon-like-peptide-1 (GLP-1) agonist, were added. In follow-up visits during the ensuing 22 months (Table 3), diabetes therapy ultimately consisted of metformin (2 g BID), liraglutide (1.8 mg QD), a subcutaneously applied GLP-1 agonist and insulin glargine (26 units QD). The SGLT-2 inhibitor was discontinued due to side effects. The HbA1c was 6.6%, body weight decreased to 94.7 kg (body-mass index: 28.0 kg/m²). Strikingly, the patient was switched from a 3-fold to a 2-fold combination of antihypertensive drugs. The corresponding daily defined dose (DDD) of antihypertensive medications changed from a DDD of 7 at hospital admission to a DDD of 2 at the last follow-up visit, 22 months after discharge. Although the insulin dose was reduced from 160 units/d to 46 units/d during the index hospitalization, further reductions were achieved during the 22 ensuing months during 9 follow-up visits (Fig. 1). The decrease of antihypertensive medication lagged behind insulin reduction and HbA1c normalization considerably. However, an ambulatory blood-pressure recordings over 24 hours after 3 months proved a normal blood pressure (mean day-time systolic blood pressure (mean day-time systolic 131 mmHg, diastolic blood pressure 88 mmHg, reverse dipper). Likewise, the patient’s mobility improved for one year following insulin reduction. For the first time in 6 years, the patient was able to leave his flat alone using a walking aid. Lastly, troponin T elevation at index hospitalization normalized with a period of 10 months following the discharge (troponin T levels dropped to 19.5 ng/L, normal reference: < 14.0). During the observation period in hospital and after discharge, a coronary angiography was not performed. After 22 months, the patient was rehospitalized for minor stroke with a fully reversible facial paresis on the right and dysphasia. Additional exams suggested a cerebral ischemic event in the cerebral media artery, proved bilateral carotid sclerosis without need for intervention. Transthoracic echocardiography revealed a normal systolic left-ventricular function, moderate left-ventricular hypertrophy and a moderate mitral stenosis. Holter electrocardiogram showed sinus rhythm and a reduced heart rate variability (standard deviation of normal beats: 64 ms). The stroke prevention was changed from Aspirin to Clopidogrel. The patient was discharged with the same diabetic and antihypertensive medication like 22 months after discharge of index hospitalization.
Table 1
Time | 2–3 h | 7–8 h | 11 h | 16–17 h | 18–19 h | 20–21 h | 22–23 h | 23–0 h |
Day 1 | | | | | | 8.9 | | |
Day 2 | | | 15.7 | 11.5 | | | 6.5 | |
Day 3 | | 11.8 | 18.9 | 10.8 | | 11.8 | | 7.5 |
Day 4 | | 11.3 | 19.9 | 11.7 | 9.5 | 12.3 | | |
Day 5 | | 16.4 | 16.7 | 16.3 | | 15.1 | 15.9 | |
Day 6 | | | 17.0 | | 9.8 | 12.3 | | |
Day 7 | | 14.9 | 13.7 | 8.3 | | 10.4 | | |
Day 8 | | 12.1 | 11.4 | 11.0 | | 11.9 | | |
Day 9 | | 12.7 | 11.3 | 10.5 | | 11.8 | | |
Day 10 | | 11.4 | 13.2 | 10.0 | | 11.0 | | |
Day 11 | | 8.9 | 10.7 | | | | | |
Table 2
Laboratory parameter | unit | Reference range | Day of admission | 22-months follow-up visit |
Sodium | mmol/l | 136–145 | 137 | 140 |
Potassium | mmol/l | 3.4–4.5 | 4.2 | 4.7 |
Calcium | mmol/l | 2.20–2.55 | 2.20 | 2.31 |
Glucose | mmol/l | 4.11–6.05 | 12.03 | 9.79 |
HbA1c | % | NA | 11.2 | 6.6 |
eGFR | ml/min/1.73m² | > 60.00 | 63.27 | 73.70 |
Creatinine | µmol/l | 62–106 | 101 | 88 |
Urea | mmol/l | 2.76–8.07 | 7.50 | 6.00 |
ASAT | µkat/l | 202.3-416.5 | 0.53 | 0.43 |
ALAT | µkat/l | 2.0–21.0 | 0.60 | 0.45 |
GGTP | µkat/l | < 5.0 | 0.67 | 0.48 |
Troponin T | ng/l | 0.17–0.85 | 34.0 | 19.5 |
NT-pro BNP | ng/l | < 125 | 174 | NA |
C-reactive protein | mg/l | < 1.00 | 1.3 | 0.4 |
Hemoglobin | mmol/l | 8.4–11.1 | 8.8 | 8.9 |
Leukocyte count | Gpt/l | 3.70–9.90 | 7.6 | 7.9 |
Platelet count | Gpt/l | 140–360 | 96 | 113 |
International normlalized ratio | | 0.85–1.15 | 1.11 | 1.05 |
Table 3
Months after hospital admis-sion (n) | Wt (kg) | Hb A1c (%) | Blood pres-sure (mmHg) | Anti-hyper-ten-sive drug classes (n) | Defined Daily Dose of anti-hyper-ten-sive Rx (n) | Daily cumulative dose of antihypertensive Rx (mg) | Daily cumulative dose of non-insulin diabetes Rx (mg) | Insulin units per day (n) |
0 | 105 | 11.2 | 161/105 | 3 | 3 + 2 + 2 | Urapidil (180), Valsartan (320), Bisoprolol (10) | NA | 160 |
0.3 | NA | NA | 151/81 | 3 | 2 + 2 | Valsartan (320), Bisoprolol (10) | Metformin (500), Empagliflozin (10), Dulaglutide (1.5/7) | 46 |
3 | NA | 6.9 | 153/88 | 3 | 1 + 2 + 2 | Moxonidine (0.6), Valsartan (320), Bisoprolol (10) | Metformin (1000), Dulaglutide (1.5/7) | 46 |
5 | NA | NA | 126/76 | 3 | 1 + 2 + 2 | Amlodipine (5), Valsartan (320), Bisoprolol (10) | Metformin (2000), Dulaglutide (1.5/7) | 42 |
8 | 96.6 | 4.9 | 106/68 | 3 | 1 + 2 + 2 | Amlodipine (5), Valsartan (320), Metoprolol (96.5) | Metformin (2000), Liraglutide (0.6) | 30 |
9 | NA | NA | 135/81 | 3 | 1 + 2 + 2 | Amlodipine (5), Valsartan (320). Metoprolol (96.5) | Metformin (2000), Liraglutide (1.2) | 30 |
12 | 95.0 | 6.2 | 150/88 | 3 | 1 + 2 + 2 | Amlodipine (5), Valsartan (320), Metoprolol (96.5) | Metformin (2000), Liraglutid (1.2) | 28 |
15 | 97.3 | 6.4 | 150/87 | 3 | 0.5 + 1 + 0.5 | Amlodipine (2.5), Valsartan (160), Bisoprolol (2.5) | Metformin (2000), Liraglutide (1.2) | 24 |
16 | NA | NA | 149/97 | 3 | 0.5 + 1 + 1 | Amlodipine (2.5), Valsartan (160), Bisoprolol (5) | Metformin (2000), Liraglutide (1.2) | 24 |
21 | NA | 6.4 | 168/94 | 2 | 1 + 1 | Valsartan (160), Bisoprolol (5) | Metformin (2000), Liraglutide (1.2) | 26 |
22 | 94.7 | 6.6 | 136/96 | 2 | 1 + 1 | Valsartan (160), Bisoprolol (5) | Metformin (2000), Liraglutide (1.8) | 26 |