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 with decreased muscle reflexes and hypopallesthesia. Electrophysiological investigation showed a sensorimotor axonal and demyelinating peripheral neuropathy. 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. 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. 4 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 (5 mg BID). At admission, 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. At admission, the HbA1c was 11.2% and the kidney function was not impaired. 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, empagliflozin, a sodium-glucose transporter-2 inhibitor (SGLT-2i), and dulaglutide, a subcutaneously applied, once-a-week glucagon-like-peptide-1 (GLP-1) agonist, were added. In follow-up visits during the ensuing 22 months following the discharge (Table 3), diabetes therapy ultimately consisted of metformin (2 g/d), the GLP-1 agonist liraglutide (1.8 mg/d) 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 as shown in Fig. 1 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, coronary angiography was not performed. Transthoracic echocardiography, performed 22 months after discharge, revealed a normal systolic left-ventricular function, moderate left-ventricular hypertrophy and a moderate mitral stenosis. 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. The stroke prevention was changed from Aspirin to Clopidogrel. Holter electrocardiogram showed sinus rhythm and a reduced heart rate variability (standard deviation of normal beats: 64 ms). The patient was discharged with the same diabetic and antihypertensive medication like 22 months after discharge of index hospitalization (Table 3).
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 |
0.5 | 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 |