HbA1c variability is independently associated with progression of diabetic kidney disease in an urban multi-ethnic cohort of people with type 1 diabetes.

AIMS/HYPOTHESIS: The role of HbA1c variability in the progression of diabetic kidney disease is unclear, with most studies to date performed in White populations and limited data on its role in predicting advanced kidney outcomes. Our aim was to evaluate if long-term intra-individual HbA1c variability is a risk factor for kidney disease progression (defined as an eGFR decline of ≥50% from baseline with a final eGFR of <30 ml/min per 1.73 m2) in an ethnically heterogeneous cohort of people with type 1 diabetes with a preserved eGFR ≥45 ml/min per 1.73 m2 at baseline. METHODS: Electronic health record data from people attending outpatient clinics between 2004 and 2018 in two large university hospitals in London were collected. HbA1c variability was assessed using three distinct methods: (1) SD of HbA1c (SD-HbA1c); (2) visit-adjusted SD (adj-HbA1c): SD-HbA1c/√n/(n-1), where n is the number of HbA1c measurements per participant; and (3) CV (CV-HbA1c): SD-HbA1c/mean-HbA1c. All participants had six or more follow-up HbA1c measurements. The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration equation and clinical/biochemical results from routine care were extracted from electronic health records. RESULTS: In total, 3466 participants (50% female, 78% White, 13% African Caribbean, 3% Asian and 6% of mixed heritage or self-reporting as 'other') were followed for a median (IQR) of 8.2 (4.2-11.6) years. Of this cohort, 249 (7%) showed kidney disease progression. Higher HbA1c variability was independently associated with a higher risk of kidney disease progression, with HRs (95% CIs) of 7.76 (4.54, 13.26), 2.62 (1.75, 3.94) and 5.46 (3.40, 8.79) (lowest vs highest HbA1c variability quartile) for methods 1-3, respectively. Increasing age, baseline HbA1c, systolic BP and urinary albumin/creatinine ratio were also associated with kidney disease progression (p<0.05 for all). African Caribbean ethnicity was associated with an increased risk of kidney disease progression (HR [95% CI] 1.47 [1.09, 1.98], 1.76 [1.32, 2.36] and 1.57 [1.17, 2.12] for methods 1-3, respectively) and this effect was independent of glycaemic variability and other traditional risk factors. CONCLUSIONS/INTERPRETATION: We observed an independent association between HbA1c variability, evaluated using three distinct methods, and significant kidney disease progression in a multi-ethnic type 1 diabetes cohort. Further studies are needed to elucidate the mechanisms that may explain our results and evaluate if HbA1c variability is a modifiable risk factor for preventing diabetic kidney disease progression.

Standards of diabetes care and burden of hypoglycaemia in people with diabetes on peritoneal dialysis: Results from a real-world clinical audit.

There is limited data on the standards of diabetes care in people on peritoneal dialysis (PD). Our aim was to assess the standards of diabetes care and the burden of hypoglycaemia in people with diabetes on PD. We performed a retrospective study at three university hospitals from December 2021 to January 2022. Clinical data were extracted from electronic health records. Diabetes care of people on PD was compared against recommended standards for people with diabetes on haemodialysis (as there are no agreed standards for PD). The degree of hypoglycaemia awareness was assessed by validated questionnaires. A total of 65 adults (15 type 1, 49 type 2 and 1 monogenic-diabetes) with a mean age of 63 (range 29-88) years were evaluated. Of them, 92% had diabetes retinal screening with annual review. In contrast, in this high-risk group for foot disease, only 77% had annual foot reviews. The rates of diabetes specialist reviews were variable between hospitals at 63-94% and 10 (15%) had impaired hypoglycaemia awareness. Of the cohort, 32% had HbA1c within the acceptable range of 58-80 mmol/mol (7.5-8.5%), 21% had HbA1c below 58 mmol/mol (7.5%) and 21% (n = 14) reported at least one hypoglycaemic event per month. Our results indicate variation of care within and between different centres, and the need for improved diabetes care in people on PD. Further work is required to establish agreed standards/recommendations of diabetes care in this population. Our findings highlight the necessity of an integrated multidisciplinary approach to improve the standard of diabetes care for people on PD.

African Caribbean Ethnicity Is an Independent Predictor of Significant Decline in Kidney Function in People With Type 1 Diabetes.

OBJECTIVE: The aim of the study was to identify the demographic and clinical features in an urban cohort of people with type 1 diabetes who developed a ≥50% decline in estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: We evaluated 5,261 people with type 1 diabetes (51% female, 13.4% African Caribbean) with baseline eGFR >45 mL/min/1.73 m2 between 2004 and 2018. The primary end point was an eGFR decline of ≥50% from baseline with a final eGFR <30 mL/min/1.73 m2. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: Of the cohort, 263 (5%) reached the primary end point. These individuals were more likely to be of African Caribbean ethnicity, be older, have a longer duration of diabetes, have higher systolic blood pressure and HbA1c, have more prevalent retinopathy, and have higher albuminuria (all P < 0.05). In multivariable Cox regression models, African Caribbean ethnicity emerged as a significant risk factor for the primary end point (hazard ratio 1.57, 95% CI 1.19, 2.08) compared with other ethnicities and independent of established risk factors (P < 0.01). The incidence rate for the primary end point in African Caribbean people was double that in non-African Caribbean people (16 vs. 7.7 per 1000 patient-years, P < 0.001). A similar significant independent impact of African Caribbean ethnicity for secondary end points (≥40% and ≥30% fall in eGFR) was observed. CONCLUSIONS: We report a novel observation that African Caribbean ethnicity increased the risk of kidney function loss in people with type 1 diabetes, an effect that was independent of traditional risk factors. Further studies are needed to examine the associated pathophysiology that may explain this observation.

Surgical Diabetic Foot Debridement: Improving Training and Practice Utilizing the Traffic Light Principle.

Comprehensive management of a severe diabetic foot infection focus on clear treatment pathways. Including rapid, radical debridement of all infection in addition to intravenous antibiotics and supportive measures. However, inexperienced surgeons can often underestimate the extent of infection, risking inadequate debridement, repeated theatre episodes, higher hospital morbidity, and hospital length of stay (LOS). This study aims to assess protocolized diabetic-foot-debridement: Red-Amber-Green (RAG) model as part of a value-based driven intervention. The model highlights necrotic/infected tissue (red-zone, nonviable), followed by areas of moderate damage (amber-zone), healthy tissue (green-zone, viable). Sequential training of orthopedic surgeons supporting our emergency service was undertaken prior to introduction. We compared outcomes before/after RAG introduction (pre-RAG, n = 48; post- RAG, n = 35). Outcomes measured included: impact on number of debridement/individual admission, percentage of individuals requiring multiple debridement, and length-of-hospital-stay as a function-of-cost. All-patients fulfilled grade 2/3, stage-B, of the Texas-Wound-Classification. Those with evidence of ischemia were excluded. The pre-RAG-group were younger (53.8 ± 11.0 years vs 60.3 ± 9.2 years, P = .01); otherwise the 2-groups were matched: HbA1c, white blood cell count, and C-reactive protein. The post-RAG-group underwent significantly lower numbers of debridement's (1.1 ± 0.3 vs 1.5 ± 0.6/individual admission, P = .003); equired fewer visits to theatre (8.6% vs 38%, P = .003), their LOS was reduced (median LOS pre-RAG 36.0 vs post-RAG 21.5 days, P = .02). RAG facilitates infection clearance, fewer theatre-episodes, and shorter LOS. This protocolized-management-tools in acute severely infected diabetic foot infection offers benefits to patients and health-care-gain.

The LDIFLARE and CCM Methods Demonstrate Early Nerve Fiber Abnormalities in Untreated Hypothyroidism: A Prospective Study.

Context: Recent studies using skin biopsy suggest presence of small-fiber neuropathy in subclinical hypothyroidism. This study uses two noninvasive methods-the laser Doppler imager flare technique (LDIFLARE) and corneal confocal microscopy (CCM)-to assess small-fiber function (SFF) and small-fiber structure (SFS), respectively, in newly diagnosed hypothyroidism (HT) before and after adequate treatment. Design and Setting: Single-center, prospective, intervention-based cohort study. Patients and Participants: Twenty patients with newly diagnosed HT (15 with primary HT and 5 with post-radioiodine HT) along with 20 age-matched healthy controls (HCs). Interventions: Patients with HT and HCs were assessed neurologically at diagnosis and baseline, respectively. The HT group was reassessed after optimal replacement (defined as TSH level of 0.27 to 4.20 mIU/L) with levothyroxine (LT4) and HCs were reviewed after 1 year. Main Outcome Measures: Neurologic assessment for small fibers was performed by using LDIFLARE for SFF and CCM for SFS; large fibers were studied by sural nerve conduction velocity (SNCV) and sural nerve amplitude (SNAP). Results: At baseline, both LDIFLARE (mean ± SD) (6.74 ± 1.20 vs 8.90 ± 1.75 cm2; P = 0.0002) and CCM nerve fiber density (CNFD) (expressed as number of fibers per mm2: 50.77 ± 6.54 vs 58.32 ± 6.54; P = 0.002) were significantly reduced in the HT group compared with HCs whereas neither SNCV nor SNAP was different (P ≥ 0.05). After optimal LT4 treatment, both LDIFLARE (7.72 ± 1.12 vs 6.74 ± 1.20 cm2; P ≤ 0.0001) and CNFD (54.43 ± 5.70 vs 50.77 ± 6.54 no./mm2; P = 0.02) improved significantly but remained significantly reduced compared to HCs (P = 0.008 and P = 0.01, respectively) despite normalization of TSH. Conclusions: This study demonstrates that dysfunction of small fibers precedes large neural fiber abnormalities in early HT. This can be reversed by replacement therapy to achieve a biochemically euthyroid state, but small-fiber neural outcomes continued to remain low compared with values in HCs.

Nutritional Supplementation for Diabetic Foot Ulcers: The Big Challenge.

Diabetic foot ulcers remain difficult to heal and nutritional supplementation may be an important complementary therapeutic measure. However, we need to clarify many issues before such supplementation is more widely used. Indeed, improvements are needed in the following areas: evaluation of nutritional inadequacy, completion of randomized controlled trials, understanding of patient and ulcer characteristics that favor response to nutritional supplementation, optimal duration of supplementation therapy, and evaluation of patient adherence. The challenge is now to acquire more knowledge in the aforementioned areas.