Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in type 1 diabetes and type 2 diabetes: Lipid goal attainment in a large German-Austrian diabetes registry.

AIM: To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid-lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022. MATERIALS AND METHODS: Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline-based low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment was analysed. RESULTS: In patients with T1D (median age 38.35 [20.51-57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86-78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk-based recommended LDL-C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk-based goal of LDL-C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non-HDL-C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively. CONCLUSION: Approximately 2 years after publication of the guidelines, LDL-C and non-HDL-C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk.

Disease heterogeneity of adult diabetes based on routine clinical variables at diagnosis: Results from the German/Austrian Diabetes Follow-up Registry.

AIM: To cluster adults with diabetes using variables from real-world clinical care at manifestation. MATERIALS AND METHODS: We applied hierarchical clustering using Ward's method to 56 869 adults documented in the prospective Diabetes Follow-up Registry (DPV). Clustering variables included age, sex, body mass index (BMI), HbA1c, diabetic ketoacidosis (DKA), components of the metabolic syndrome (hypertension/dyslipidaemia/hyperuricaemia) and beta-cell antibody status. Time until use of oral antidiabetic drugs (OADs), use of insulin, chronic kidney disease (CKD), cardiovascular disease (CVD), retinopathy or neuropathy were assessed using Kaplan-Meier analysis and Cox regression models. RESULTS: We identified eight clusters: four clusters comprised early diabetes onset (median age 40-50 years) but differed with regard to BMI, HbA1c, DKA and antibody positivity. Two clusters included adults with diabetes onset aged in their early 60s who met target HbA1c, but differed in BMI and sex distribution. Two clusters were characterized by late diabetes onset (median age 69 and 77 years) and comparatively low BMI, but differences in HbA1c. Earlier insulin use was observed in adults with high HbA1c, and earlier OAD use was observed in those with high BMI. Time until CKD or CVD was shorter in those with late onset, whereas retinopathy occurred earlier in adults with late onset and high HbA1c, and in adults with early onset, but high HbA1c and high percentage of antibody positivity. CONCLUSIONS: Adult diabetes is heterogeneous beyond classical type 1/type 2 diabetes, based on easily available variables in clinical practice using an automated clustering algorithm that allows both continuous and binary variables.

Factors associated with diabetic foot ulcers and lower limb amputations in type 1 and type 2 diabetes supported by real-world data from the German/Austrian DPV registry.

AIMS: Diabetic foot ulcer (DFU) is a leading cause of lower limb amputations in people with diabetes. This study was aimed to retrospectively analyze factors affecting DFU using real-world data from a large, prospective central-European diabetes registry (DPV [Diabetes-Patienten-Verlaufsdokumentation]). MATERIALS AND METHODS: We matched adults with type 1 (T1D) or type 2 diabetes (T2D) and DFU to controls without DFU by diabetes type, age, sex, diabetes duration, and treatment year to compare possible risk factors. Cox regression was used to calculate hazard ratios for amputation among those with DFU. RESULTS: In our cohort (N = 63 464), male sex, taller height, and diabetes complications such as neuropathy, peripheral artery disease, nephropathy, and retinopathy were associated with DFU (all p < .001). Glycated hemoglobin (HbA1c) was related to DFU only in T1D (mean with 95% confidence interval [CI]: 7.8 [6.9-9.0] % vs 7.5 [6.8-8.5] %, p < .001). High triglycerides and worse low-density lipoprotein/high-density lipoprotein ratio were also associated with DFU in T1D, whereas smoking (14.7% vs 13.1%) and alcohol abuse (6.4% vs 3.8%, both p < .001) were associated with DFU in T2D. Male sex, higher Wagner grades, and high HbA1c in both diabetes types and insulin use in T2D were associated with increased hazard ratios for amputations. CONCLUSIONS: Sex, body height, and diabetes complications were associated DFU risk in adults with T1D and T2D. Improvement in glycemic control and lipid levels in T1D and reduction of smoking and drinking in T2D may be appropriate interventions to reduce the risk for DFU or amputations.

Dynamics of Hemoglobin A1c, Body Mass Index, and Rates of Severe Hypoglycemia in 4434 Adults with Type 1 or Type 2 Diabetes After Initiation of Continuous Glucose Monitoring.

Background: Continuous glucose monitoring (CGM) might have beneficial effects on glycemic control and body mass index (BMI) in adults with type 1 (T1D) or type 2 diabetes (T2D). Methods: The diabetes prospective follow-up registry was used to identify individuals with T1D or T2D ≥18 years starting CGM management in 2015 or later and follow-up information available. Hemoglobin A1c (HbA1c), BMI, and event rates of severe hypoglycemia in the year before CGM start were compared with two follow-up periods: (1) CGM use for 3-6 months and (2) CGM use for >6 months. Repeated measurements linear and negative binomial regressions were used (adjustment for sex, age at diabetes onset, and baseline parameters) and stratified by diabetes type. Results: Mean follow-up time was 1.8 years in T1D (n = 2994) and 1.9 years in T2D (n = 1440). In T1D, adjusted mean HbA1c decreased significantly from 7.65% (95% confidence interval: 7.62-7.68) at baseline to 7.54% (7.51-7.57) during follow-up. BMI increased slightly (baseline: 25.4 kg/m2 [25.3-25.5], follow-up >6 months: 25.8 kg/m2 [25.7-25.9]), whereas event rates of severe hypoglycemia were significantly lower after >6 months with CGM (9.0 events/100 patient-years [PY; 8.0-10.1]) compared with baseline (11.3 events/100 PY [10.4-12.2]) in adults with T1D. In T2D, HbA1c decreased from 7.21% (7.17%-7.25%) to 7.00% (6.95%-7.04%) and BMI did not change after CGM initiation. Conclusion: Our results provide real-world evidence on CGM management in adult individuals with T1D or T2D. We suggest strengthening patients' and physicians' readiness toward diabetes technology in T2D and more openness of health insurance to cover cost based on proven benefits.

A comparison of the rapid-acting insulin analogue glulisine with lispro and aspart for the pump treatment of patients with type 1 diabetes.

AIMS: (1) To describe the population of patients with type 1 diabetes (T1DM) using the rapid-acting insulin analogue glulisine versus lispro and aspart during continuous subcutaneous insulin infusion (CSII); (2) to describe insulin relative effectiveness based on hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and dose; (3) to determine rates of hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA). METHODS: The analysis used March 2021 data from the Diabetes-Patienten-Verlaufsdokumentation registry, which contains data of 618,903 patients with diabetes. Patients were propensity-matched by age, sex, and diabetes duration. RESULTS: Overall, 42,736 patients of any age were eligible for analysis based on insulin pump usage with either glulisine (N = 707) or lispro/aspart (N = 42,029) between 2004 and 2020. Patients receiving glulisine were older (median 20.0 vs. 16.2 years), equally often male (47.2% vs. 47.8%) and had a longer diabetes duration (median 9.4 vs. 7.4 years). After propensity score matching, 707 pairs remained (total N = 1414). Patient characteristics between groups were similar. Achieved HbA1c values were also comparable: 8.04%, 64 mmol/mol versus 7.96%, 63 mmol/mol for glulisine and lispro/aspart [LS mean difference 0.08 (95%CI - 0.08, 0.25)]. FBG was 9.37 mmol/L (168.9 mg/dL) and 9.58 mmol/L (172.6 mg/dL) in the glulisine and lispro/aspart groups [LS mean diff. - 0.21; (95%CI - 1.13, 0.72)]. Total daily insulin doses and prandial to total insulin ratios were also similar. Glulisine group patients had higher rates of lipodystrophy (0.85% vs. 0.71%) (LS mean diff. 0.18 [95% CI - 1.01, 1.38]) and non-severe DKA (3.11% vs. 0.57%; p = 0.002). Fewer patients in the glulisine group had severe hypoglycemic events (7.66 vs. 9.09; p = 0.333) and severe ketoacidosis events (0.57% vs. 1.56%; p = 0.082) but more had hypoglycemic coma events (p = 0.773), although the differences were not statistically significant. CONCLUSIONS: Insulin glulisine had comparable glucose control to lispro/aspart. The use of glulisine was less frequent in the present analysis compared to the previous trials.

Hypoglycemia in Older Adults: Time Trends and Treatment Differences in Patients Aged ≥75 Years With Type 2 Diabetes.

OBJECTIVES: Hypoglycemia is a potentially life-threatening drug event under antidiabetic treatment. The aim of the study was to examine time trends in severe hypoglycemia in older adults with type 2 diabetes mellitus (T2DM) and antidiabetic treatment. DESIGN: Multicenter prospective diabetes patient follow-up registry (DPV). SETTING AND PARTICIPANTS: Patients aged ≥75 years with T2DM and documented treatment between 2005 and 2019. METHODS: Outcomes of interest were rates of severe hypoglycemia, diabetes therapy, body mass index, HbA1c, and estimated glomerular filtration rate. Time trends of outcomes were analyzed in the whole cohort and compared between age groups (75-<80, 80-<85, ≥85 years). RESULTS: A total of 136,931 patients from 188 diabetes centers were included. The adjusted HbA1c decreased from 7.3% (95% confidence interval 7.3-7.4) in 2005 to 7.2% (7.2-7.2) in 2019 (P < .001), with no significant difference between age groups (P = .47). Rates of severe hypoglycemia decreased from 6.7 (6.0-7.4) to 4.1 of 100 person-years (3.7-4.5) (P < .001) in the entire population. Patients aged ≥85 years had constantly lower HbA1c levels compared with younger groups (P < .001). Although severe hypoglycemia decreased the most in the ≥85 age group (P < .001), severe hypoglycemia remained consistently higher in this group compared with the 75 to <80 years group (P < .001). CONCLUSIONS AND IMPLICATIONS: During the analyzed time, the risk for severe hypoglycemia decreased. Although drugs with intrinsic risk for hypoglycemia were used less frequently, antidiabetic treatment in older adults should be further improved to continue reducing severe hypoglycemia in this age group, potentially accepting less strict metabolic control and age-specific target ranges.

Continuous Glucose Monitoring in Adults with Type 1 Diabetes: Real-World Data from the German/Austrian Prospective Diabetes Follow-Up Registry.

Background: To analyze key indicators of metabolic control in adults with type 1 diabetes (T1D) using real-time or intermittent scanning continuous glucose monitoring (rtCGM/iscCGM) during real-life care, based on the German/Austrian/Swiss Prospective Diabetes Follow-up (DPV) registry. Methods: Cross-sectional analysis including 233 adults with T1D using CGM. We assessed CGM metrics by gender, age group (18 to <30 years vs. ≥30 years), insulin delivery method (multiple daily injections vs. continuous subcutaneous insulin infusion [CSII]) and sensor type (iscCGM vs. rtCGM), working days versus weekends, and daytime versus night-time using multivariable linear regression models (adjusted for demographic variables) or Wilcoxon signed-rank test. Results: Overall, 79/21% of T1D patients used iscCGM/rtCGM. Those aged ≥30 years spent more time in range (TIR [70-180 mg/dL] 54% vs. 49%) and hypoglycemic range <70 mg/dL (7% vs. 5%), less time in hyperglycemic range >180 mg/dL (38% vs. 46%) and had a lower glucose variability (coefficient of variation [CV] 36% vs. 37%) compared with adults aged <30 years. We found no significant differences between genders. Multivariable regression models revealed the highest Time In Range (TIR) and lowest time with sensor glucose >250 mg/dL, CV and daytime-night-time differences in those treated with CSII and rtCGM. Glucose profiles were slightly more favorable on working days. Conclusions: In our real-world data, rtCGM versus iscCGM was associated with a higher percentage of TIR and improved metabolic stability. Differences in ambulatory glucose profiles on working and weekend days may indicate lifestyle habits affecting glycemic stability. Real-life CGM results should be included in benchmarking reports in addition to hemoglobin A1c (HbA1c) and history of hypoglycemia.

Risk factors for decline in renal function among young adults with type 1 diabetes.

AIMS: To investigate risk factors for declining renal function among subjects with type-1-diabetes. METHODS: Observational study based on data from the diabetes registry DPV. 4424 type-1-diabetes subjects aged ≥18 years, age at onset <18 years were identified. Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (eGFR). Annual rate of renal decline was estimated for each patient using hierarchic linear regression models. Additional regression models were fitted to adjust for covariates. RESULTS: Median age was 26 [Q1; Q3: 21; 39] years. Annual decline of renal function was -1.22 (95% CI: -1.50; -0.94) ml/min/1.73 m2. At baseline, higher eGFR was related to more rapid decline compared to impaired or reduced eGFR (GFR ≥ 90: -2.06 (-2.35; -1.76), 60 ≤ GFR < 90: 0.45 (0.08; 0.81), GFR < 60: 0.52 (-0.24; 1.29) ml/min/1.73 m2, p < 0.01). During follow-up, the highest decline was associated with reduced renal function, whereas the lowest decline was related to normal kidney function (p < 0.01). Poor metabolic control (p = 0.04), hypertension (p < 0.01) and albuminuria (p = 0.03) were associated with more rapid loss of kidney function. No difference was observed among insulin regimen. CONCLUSION: Among this large type-1-diabetes cohort, more rapid loss of kidney function was related to higher baseline eGFR, log-term worse metabolic control and diabetic comorbidities.

The role of limited joint mobility in diabetic patients with an at-risk foot.

OBJECTIVE: To assess the role of limited joint mobility (LJM) in causing abnormal high plantar pressures in the forefoot of diabetic patients with an at-risk foot. RESEARCH DESIGN AND METHODS: A total of 70 type 1 or type 2 diabetic patients and 30 control subjects participated in this cross-sectional study. Thirty-five diabetic patients with an at-risk foot, defined as a foot with neuropathy but without ulceration or previous ulceration, and 35 diabetic control subjects without neuropathy were selected for the subgroups. Joint mobility was assessed in the foot at the ankle and metatarsophalangeal I (first MTP) joints. Using the FastScan plantar pressure analyzer, the pressure-time integrals (PTIs) as dynamic variables were measured in each foot. The clinical assessment included standard measures of peripheral neuropathy. RESULTS: The mobility at the ankle and first MTP joint were significantly reduced in the foot-at-risk group compared with the diabetic control group and the control subjects (P < 0.0001). The PTIs were significantly higher in the foot-at-risk group compared with the two other groups (P < 0.0001). There was a strong inverse correlation between the mobility of the ankle or first MTP joint and the PTI of the diabetic patients (r = -0.67, P < 0.0001, and r = -0.71, P < 0.0001, respectively). The vibration perception threshold was positively correlated with the PTI of the diabetic patients (r = 0.44, P = 0.0001). CONCLUSIONS: Diabetic patients with an at-risk foot have reduced joint mobility and elevated PTIs on the plantar forefoot, placing them at risk for subsequent ulceration. Therefore, LJM may be a possible factor in causing high plantar pressures and may contribute to foot ulceration in the susceptible neuropathic at-risk foot.

Psoriasis and Diabetes: A Multicenter Study in 222078 Type 2 Diabetes Patients Reveals High Levels of Depression.

OBJECTIVE: This study aimed to investigate the association between psoriasis and disease outcome in type 2 diabetes (T2D). METHODS: 222078 T2D patients (≥10 years old) from the prospective, multicenter diabetes patient registry were analyzed. Specific search items were used to identify psoriasis patients. Multiple regression models were fitted and adjusted for demographic confounder. RESULTS: 232 T2D patients had comorbid psoriasis. After adjusting psoriasis patients revealed a higher BMI (31.8 [31.0; 32.6] versus 30.6 [30.5; 30.6] kg/m2, p = 0.004) and HbA1c (64.8 [62.1; 67.6] versus 59.0 [58.9; 59.1] mmol/mol, p < 0.0001). Insulin was used more frequently (62.3 [55.7; 68.5] versus 50.9 [50.7; 51.1] %, p = 0.001), only OAD/GLP-1 was similar, and nonpharmacological treatment was less common (13.3 [9.5; 18.3] versus 21.9 [21.7; 22.1] %, p = 0.002). Severe hypoglycemia (0.31 [0.238; 0.399] versus 0.06 [0.057; 0.060] events per patient-year, p < 0.0001), hypertension (86.1 [81.1; 90.0] versus 68.0 [67.8; 68.2] %, p < 0.0001), and thyroid disease (14.0 [10.1; 19.2] versus 4.6 [4.5; 4.7] %, p < 0.0001) were more prevalent. Depression occurred more often (10.5 [7.1; 15.2] versus 2.8 [2.7; 2.8] %, p < 0.0001). CONCLUSIONS: Clinical diabetes characteristics in psoriasis T2D patients were clearly worse compared to patients without psoriasis. Comorbid conditions and depression were more prevalent, and more intensive diabetes therapy was required.

Impact of Physical Activity on Glycemic Control and Prevalence of Cardiovascular Risk Factors in Adults With Type 1 Diabetes: A Cross-sectional Multicenter Study of 18,028 Patients.

OBJECTIVE: Physical activity (PA) can improve cardiovascular risk in the general population and in patients with type 2 diabetes. Studies also indicate an HbA(1c)-lowering effect in patients with type 2 diabetes. Since reports in patients with type 1 diabetes are scarce, this analysis aimed to investigate whether there is an association between PA and glycemic control or cardiovascular risk in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 18,028 adults (≥18 to <80 years of age) from Germany and Austria with type 1 diabetes from the Diabetes-Patienten-Verlaufsdokumentation (DPV) database were included. Patients were stratified according to their self-reported frequency of PA (PA0, inactive; PA1, one to two times per week; PA2, more than two times per week). Multivariable regression models were applied for glycemic control, diabetes-related comorbidities, and cardiovascular risk factors. Data were adjusted for sex, age, and diabetes duration. P values for trend were given. SAS 9.4 was used for statistical analysis. RESULTS: An inverse association between PA and HbA(1c), diabetic ketoacidosis, BMI, dyslipidemia (all P < 0.0001), and hypertension (P = 0.0150), as well as between PA and retinopathy or microalbuminuria (both P < 0.0001), was present. Severe hypoglycemia (assistance required) did not differ in PA groups (P = 0.8989), whereas severe hypoglycemia with coma was inversely associated with PA (P < 0.0001). CONCLUSIONS: PA seemed to be beneficial with respect to glycemic control, diabetes-related comorbidities, and cardiovascular risk factors without an increase of adverse events. Hence, our data underscore the recommendation for subjects with type 1 diabetes to perform regular PA.

Determinants and estimation of healing times in diabetic foot ulcers.

AIMS: To assess the wound size reduction and time course for healing and to establish equations to predict the time course of wound healing in neuropathic, neuroischemic, and ischemic diabetic foot ulcers. METHODS: This prospective study evaluates wound healing over at least a 10-week period in 31 Type 1 or Type 2 diabetic patients with plantar foot ulcers. Thirteen consecutive diabetic patients with neuropathic foot ulceration, 10 consecutive diabetic patients with neuroischemic ulceration, and 8 diabetic patients with peripheral occlusive vascular disease were selected for the study. All patients received identical ulcer wound care including use of proper footwear, non-weight-bearing limb support, use of appropriate antibiotics, debridement, tight control of serum glucose levels, and careful monitoring of the ulcer. Ulcer healing was assessed by planimetric measurement of the wound area every second week until wound healing. The time course of wound healing was calculated by the daily wound radius reduction. RESULTS: The wound area (mean+/-S.E.) in the patients with neuropathic foot ulceration was 61.2+/-17.1 at the beginning and 3.2+/-1.5 mm(2) after 70 days (P=.005). The wound radius decreased by 0.045 mm (95% confidence interval [CI] 0.039-0.055) per day, with most of the wound healing being achieved between the first and seventh week of ulcer care. The average healing time was 77.7 (95% CI 62-93) days. In the neuroischemic group, the initial average wound area was 26.6+/-7.0 mm(2), and 6.25+/-1.7 mm(2) after 10 weeks (P=.007). The wound radius reduction was 0.019 mm/day (95% CI 0.017-0.023) with an average healing time of 123.4 (95% CI 101-145) days. The diabetic patients with peripheral occlusive vascular disease had an average wound size of 32.6+/-13.1 at the beginning and 23.9+/-10.7 mm(2) after 70 days of ulcer care (P=.06). The daily wound radius reduction was 0.0065 mm (95% CI 0.0039-0.0091). Average ulcer duration was 133 (95% CI 116-149) days, but three of eight patients achieved no wound healing. CONCLUSIONS: Providing standard care, the time course of wound healing in diabetic foot ulcers is predominantly determined by etiologic factors, and less by wound size. Taking wound etiology and wound radius into account, the expected healing time can reliably be estimated in neuropathic and neuroischemic ulcers.