Cardiovascular events after a dramatic reduction of HbA1c in hospitalized subjects with type 2 diabetes and high long-term glucose exposure.

OBJECTIVE: In long-lasting diabetes, a dramatic reduction of HbA1c can precede adverse events such as worsening retinopathies or painful neuropathies. We have now analyzed its possible link with later cardiovascular events in subjects with type 2 diabetes, according to their long-term glucose exposure evaluated by skin autofluorescence (SAF) measured with an AGE-READER (Diagnoptics, Groningen, The Netherland). RESEARCH DESIGN AND METHODS: We studied retrospectively a cohort of patients hospitalized for uncontrolled and/or complicated type 2 diabetes from 2009 to 2017. A previous dramatic reduction of HbA1c was defined by more than -1.5 %/4 months, and later cardiovascular events as myocardial infarction, stroke, revascularization procedures, and cardiovascular-related death. Survival analyses were performed before and after categorizing the subjects for their SAF. RESULTS: The 386 subjects were 57.5 % men, 62 ± 9 years old, with a 14 ± 9 years duration of diabetes, most were treated by insulin (63.7 %). The dramatic HbA1c reducers (-3.0 ± 1.5 %) represented 16.5 % of the population. During the 51 months (IQR: 30-71) of follow-up, 53 cardiovascular events occurred and were related to the SAF (2.70 ± 0.64 AUs). Linkage was established between the SAF, the reduction of HbA1c and the cardiovascular events (p = 0.017). With a SAF higher than the median (2.65 AUs), the dramatic reduction of HbA1c was related to later cardiovascular events (HR: 3.84, 95%CI: 1.68-8.76). CONCLUSIONS: A dramatic decline of HbA1c leads to a higher risk of cardiovascular events in hospitalized subjects with type 2 diabetes and a high long-term glucose exposure.

Skin autofluorescence predicts cancer in subjects with type 2 diabetes.

INTRODUCTION: Subjects with type 2 diabetes have an excess risk of cancer. The potential role of advanced glycation end products (AGEs) accumulated during long-term hyperglycemia in cancer development has been suggested by biological studies but clinical data are missing. AGEs can be estimated by measuring the skin autofluorescence. We searched whether the skin autofluorescence could predict new cancers in persons with type 2 diabetes. RESEARCH DESIGN AND METHODS: From 2009 to 2015, we measured the skin autofluorescence of 413 subjects hospitalized for uncontrolled or complicated type 2 diabetes, without any history of cancer. The participants were followed for at least 1 year and the occurrences of new cancers were compared according to their initial skin autofluorescences. RESULTS: The participants were mainly men (57.9%), with poorly controlled (HbA1c 72±14 mmol/mol or 8.7%±1.8%) and/or complicated type 2 diabetes. Their median skin autofluorescence was 2.6 (2.2-3.0) arbitrary units. Forty-five new cancer cases (10.9%) were registered during 4.8±2.3 years of follow-up: 75.6% of these subjects had skin autofluorescence higher than the median (χ2: p=0.001). By Cox regression analysis adjusted for age, gender, body mass index, history of smoking and renal parameters, skin autofluorescence >2.6 predicted a 2.57-fold higher risk of cancer (95% CI 1.28 to 5.19, p=0.008). This association remained significant after excluding the eight cancers that occurred in the 4 years after inclusion (OR 2.95, 95% CI 1.36 to 6.38, p=0.006). As a continuous variable, skin autofluorescence was also related to new cancers (OR 1.05, 95% CI 1.01 to 1.10, p=0.045). CONCLUSIONS: Skin autofluorescence, a potential marker of glycemic memory, predicts the occurrence of cancer in subjects with type 2 diabetes. This relation provides a new clinical argument for the role of AGEs in cancer. Their estimation by measuring the skin autofluorescence may help select subjects with diabetes in cancer screening programs.

For diabetic type 1 patients, the skin autofluorescence predicts ulcers and amputations.

We searched whether the accumulation of Advanced Glycation End-products (AGEs), reflected by the skin autofluorescence (SAF), could predict diabetic foot ulcers (DFUs) during the long-term follow-up of people with type 1 diabetes. During year 2009, we measured the SAF with an AGE-Reader in 206 subjects with type 1 diabetes. DFU and amputations were registered during the 10 following years. The relation between the SAF and later DFU was analyzed by Cox model regression, adjusted for vascular risk factors. The 206 participants were mainly men (55.8%), 51 ±â€¯15 years old, with a 22 ±â€¯13 years diabetes duration. Twelve subjects presented a DFU. Their SAF were higher: 2.61 ±â€¯0.89 AU vs 2.11 ±â€¯0.53 for the others (p = 0.003), related to the risk of DFU (OR:3.69; 95% CI: 1.06-12.79) after adjustment for age, gender, diabetes duration, initial HbA1c, arterial hypertension, history of smoking, blood lipids and use of a statin. Five subjects were amputated, also related to the initial SAF: OR: 11.28 (95% CI: 1.76-79.97) after adjustment for age, gender, duration of diabetes, and HbA1c. The SAF has already been related to diabetic neuropathy and peripheral arterial disease. It predicts DFU in type 1 diabetes, which suggests that AGEs play a role in this highly specific and feared complication.

Relationship Between Diabetic Retinopathy Stages and Risk of Major Lower-Extremity Arterial Disease in Patients With Type 2 Diabetes.

OBJECTIVE: We evaluated the association between diabetic retinopathy stages and lower-extremity arterial disease (LEAD), its prognostic value, and the influence of potential contributors to this relationship in a prospective cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Diabetic retinopathy was staged at baseline as absent, nonproliferative, or proliferative. A Cox regression model was fitted in order to compute the hazard ratio (HR) (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. The retinopathy-LEAD association was assessed in subgroups by age, sex, diabetes duration, HbA1c, systolic blood pressure, diabetic kidney disease, smoking, and macrovascular disease at baseline. The performance of retinopathy in stratifying LEAD risk was assessed by using the C statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS: Among 1,320 participants without a history of LEAD at baseline, 94 (7.1%) developed a major LEAD during a 7.1-year median follow-up (incidence rate 9.6 per 1,000 person-years [95% CI 7.8-11.7]). The LEAD incidence rate (per 1,000 person-years) increased as retinopathy worsened: it was 5.5 (95% CI 3.9-7.8) in participants in whom retinopathy was absent, 14.6 (11.1-19.3) in those with nonproliferative retinopathy, and 20.1 (11.1-36.3) in those with proliferative retinopathy. Nonproliferative retinopathy (adjusted HR 2.31 [95% CI 1.43-3.81], P = 0.0006) and proliferative retinopathy (3.14 [1.40-6.15], P = 0.007) remained associated with major LEAD. No heterogeneity was observed across subgroups. Retinopathy enhanced the C statistic (+0.023 [95% CI 0.003-0.044], P = 0.02), IDI (0.209 [0.130-0.321], P < 0.001), and NRI (0.562 [0.382-0.799], P < 0.001) values for risk of LEAD, beyond traditional risk factors. CONCLUSIONS: An independent dose-response relationship was identified between diabetic retinopathy stages and major LEAD. Retinopathy yielded incremental prognostic information for stratifying risk of LEAD, suggesting its usefulness as a predictor of LEAD.

Previous dramatic reduction of HbA1c and retinopathy in Type 2 Diabetes.

AIMS: Does Diabetic Retinopathy (DR) relate to a previous dramatic reduction of HbA1c in Type 2 Diabetes (T2D)? METHODS: In patients hospitalized for T2D, we collected HbA1c values from previous years, and we defined "Rapid declinors" by a more than -3% reduction between two consecutive HbA1c, and "sustained moderate declinors" by HbA1c declining less than -3%. We analyzed the relation between DR and previous HbA1c courses, adjusted for other risk factors. RESULTS: Our 680 patients had a mean HbA1c at 8.7 ±â€¯1.7% at admission and 8.7 ±â€¯1.8 to 9.0 ±â€¯2.2% during previous years (1500 HbA1C values collected), and 24% had a DR. A previous rapid decline of HbA1c occurred in 13.5% of subjects and related to DR (OR = 1.86, 95%CI:1.02-3.40), especially proliferative (OR = 2.64, 95%CI:1.02-6.80), after adjustment for age, gender, body mass index, arterial hypertension and diabetic kidney disease, blood lipids and statin treatment, duration of diabetes and mean previous HbA1c. A previous moderate reduction of HbA1c as occurred in 28.3% other subjects was not related to DR. CONCLUSIONS: In subjects hospitalized for T2D, a previous rapid decline of HbA1c was related to proliferative DR, whereas a sustained moderate decline appeared to be safe.