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2.
J Int Med Res ; 51(11): 3000605231210403, 2023 Nov.
Article En | MEDLINE | ID: mdl-37940619

AIMS: To provide an overview of reported cases of new-onset type 1 diabetes mellitus (T1D) following COVID-19 infection. METHODS: PubMed and Scopus library databases were screened for relevant case reports published between January 2020 and June 2022. Study design, geographic region or language were not restricted. RESULTS: Twenty studies were identified and involved 37 patients (20 [54%] male, 17 [46%] female). Median age was 11.5 years (range 8 months-33 years) and 31 (84%) patients were aged ≤17 years. Most patients (33, 89%) presented with diabetic ketoacidosis (DKA). In total, 23 (62%) patients presented at the time of positive COVID-19 testing and 14 (38%) had symptoms consistent with COVID-19 infection or a previous positive test (1-56 days). Diabetes symptomatology was provided in 22 cases and (19, 86%) reported polyuria, polydipsia, polyphagia, fatigue, or weight loss or a combination of the aforementioned in the preceding weeks (3 days-12 weeks). Of the 28 patients that had data on acute and long-term treatment, all recovered well and most were managed with basal bolus insulin regimens. Quality assessment showed that most reports were either 'good' or 'moderate quality'. CONCLUSIONS: Although uncommon, new-onset T1D is a condition healthcare professionals may expect to see following a COVID-19 infection.


COVID-19 , Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Female , Humans , Infant , Male , COVID-19/complications , COVID-19 Testing , Diabetes Mellitus, Type 1/complications , Diabetic Ketoacidosis/etiology , Polyuria , Case Reports as Topic
3.
Perit Dial Int ; : 8968608231195492, 2023 Sep 13.
Article En | MEDLINE | ID: mdl-37702352

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.

4.
Article En | MEDLINE | ID: mdl-37584383

Summary: A Caucasian man in his 60s with recent diagnosis of metastatic renal cell carcinoma presented to the emergency department with a 5-day history of severe polyuria, polydipsia and fatigue and 1-day history of confusion, abdominal pain, nausea and vomiting. Investigations revealed an overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS). He had received the first dose of immunotherapy with nivolumab and ipilimumab 3 weeks prior to this attendance. New-onset type 1 diabetes (T1DM) was confirmed based on the clinical features at presentation, seropositivity for glutamic acid decarboxylase antibodies and significant insulin deficiency. He is currently on a multiple daily injections of insulin and uses intermittent-scanned glucose monitoring. Given the irreversible impact on beta-cell function and clinical response with insulin resulting in improved diabetes control, immunotherapy was resumed for his metastatic cancer with good radiological response. Although rare, new-onset T1DM can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes. Learning points: Although rare, new onset of T1DM after immunotherapy can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes and normal glycaemic parameters. Due to the irreversible destruction of beta-cells, treatment with steroids is not indicated in contrast to other settings such as immunotherapy-induced hypophysitis. Presence of low c-peptide levels post-acute presentation is indicative of an irreversible impact on beta-cell function and supports resuming immunotherapy given the significant benefits on cancer prognosis. Clinicians must maintain a high index of suspicion in regards to diagnosis and management of new-onset type 1 diabetes and advice patients on reporting symptoms suggestive of diabetes and/or diabetes-related hyperglycaemic emergencies.

5.
Kidney Int Rep ; 8(7): 1380-1388, 2023 Jul.
Article En | MEDLINE | ID: mdl-37441489

Introduction: Aortic pulse wave velocity (Ao-PWV) predicts cardiovascular and kidney disease in type 2 diabetes (T2D). Klotho is a circulating antiaging hormone (sKlotho) with putative cardiorenal protective effects. The relationship between sKlotho and Ao-PWV in diabetic kidney disease (DKD) is unknown. Methods: In a cross-sectional cohort study, the correlation of sKlotho measured by a validated immunoassay, and Ao-PWV measured by applanation tonometry, was investigated in 172 participants with T2D and early stage DKD (all had estimated glomerular filtration rate [eGFR] >45 ml/min) on stable renin angiotensin system (RAS) inhibition. In cultured human aortic smooth muscle cells (HASMCs) stimulated with angiotensin II (AngII), the effects of recombinant human sKlotho pretreatment were assessed on intracellular calcium ([Ca2+]i) responses and expression of proteins associated with proosteogenic HASMC phenotypes. Results: Mean (range) age of the cohort was 61.3 years (40-82) and 65% were male. Mean (±SD) Ao-PWV was 11.4 (±2.3) m/s, eGFR 78.8 (±23.5) and median (interquartile range) sKlotho of 358.5 (194.2-706.3) pg/ml. In multivariable linear regression analyses, we observed a statistically significant inverse relationship between sKlotho and Ao-PWV, which was independent of clinical risk factors for cardiorenal disease. Pretreatment of cultured HASMC with sKlotho significantly attenuated AngII-stimulated [Ca2+]i transients and reduced osteogenic collagen (Col1a2) expression. Conclusions: In individuals with T2D and early DKD, lower levels of sKlotho are associated with increased Ao-PWV. Taken together with the direct effect of sKlotho on mediators of aortic wall stiffness in vitro, these findings may explain the enhanced risk of cardiorenal disease in DKD.

6.
Arch. bronconeumol. (Ed. impr.) ; 59(6): 370-376, jun. 2023. ilus
Article En | IBECS | ID: ibc-221389

Background and aim: Continuous Positive Airway Pressure (CPAP) is the most effective therapy for symptomatic obstructive sleep apnoea (OSA). However, uncertainty remains about the effectiveness of CPAP in improving OSA-related metabolic dysregulation. This meta-analysis of randomized controlled trials (RCTs) aimed to investigate whether CPAP, compared to other control treatments, could improve glucose or lipid metabolism in OSA patients. Methods: Relevant articles were searched in three different databases (MEDLINE, EMBASE and Web of Science) from inception to 6th Feb 2022 through specific search terms and selection criteria. Results: From a total of 5553 articles, 31 RCTs were included. CPAP modestly improved insulin sensitivity as determined by mean fasting plasma insulin and Homeostasis Model Assessment of Insulin Resistance reduction of 1.33mU/L and 0.287, respectively. In subgroup analyses pre-diabetic/type 2 diabetic patients as well as those with sleepy OSA showed a greater response to CPAP. Regarding lipid metabolism, CPAP was associated with a mean total cholesterol reduction of 0.064mmol/L. In subgroup analyses, the benefit was higher in patients that showed more severe OSA and oxygen desaturations at the baseline sleep study as well as in younger and obese subjects. Neither glycated haemoglobin nor triglycerides, HDL- and LDL-cholesterol were reduced by CPAP. Conclusion: CPAP treatment may improve insulin sensitivity and total cholesterol levels in OSA patients but with low effect size. Our results suggest that CPAP does not substantially improve metabolic derangements in an unselected OSA population, but the effect may be higher in specific subgroups of OSA patients. (AU)


Humans , Insulin Resistance , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Continuous Positive Airway Pressure , Randomized Controlled Trials as Topic , Glucose , Triglycerides , Cholesterol
7.
J Diabetes Investig ; 14(7): 917-920, 2023 Jul.
Article En | MEDLINE | ID: mdl-37191402

We share our experience of using continuous subcutaneous insulin infusion (CSII) therapy and diabetes technology in six people (5 men) with type 1 diabetes (mean duration 36 years), who developed hyperglycemia post-simultaneous kidney/pancreas (n = 5) or pancreas only (n = 1) transplant. All were on immunosuppression and multiple daily injections of insulin prior to CSII. Four people were started on automated insulin delivery, and two people on CSII and intermittently scanned continuous glucose monitoring. With diabetes technology, the median time in range glucose improved from 37% (24-49%) to 56.6% (48-62%), and similarly, glycated hemoglobin fell from 72.7 mmol/mol (72-79 mmol/mol) to 64 mmol/mol (42-67 mmol/mol; P < 0.05 for both) with no concomitant increase in hypoglycemia. Use of diabetes technology improved glycemic parameters in people with type 1 diabetes with failing pancreatic graft function. Early use of such technology should be considered to improve diabetes control in this complex cohort.


Diabetes Mellitus, Type 1 , Hyperglycemia , Male , Humans , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/surgery , Hypoglycemic Agents/therapeutic use , Blood Glucose Self-Monitoring , Blood Glucose , Insulin/therapeutic use , Hyperglycemia/drug therapy , Hyperglycemia/etiology , Hyperglycemia/prevention & control , Pancreas , Kidney
8.
Arch Bronconeumol ; 59(6): 370-376, 2023 Jun.
Article En, Es | MEDLINE | ID: mdl-37024342

BACKGROUND AND AIM: Continuous Positive Airway Pressure (CPAP) is the most effective therapy for symptomatic obstructive sleep apnoea (OSA). However, uncertainty remains about the effectiveness of CPAP in improving OSA-related metabolic dysregulation. This meta-analysis of randomized controlled trials (RCTs) aimed to investigate whether CPAP, compared to other control treatments, could improve glucose or lipid metabolism in OSA patients. METHODS: Relevant articles were searched in three different databases (MEDLINE, EMBASE and Web of Science) from inception to 6th Feb 2022 through specific search terms and selection criteria. RESULTS: From a total of 5553 articles, 31 RCTs were included. CPAP modestly improved insulin sensitivity as determined by mean fasting plasma insulin and Homeostasis Model Assessment of Insulin Resistance reduction of 1.33mU/L and 0.287, respectively. In subgroup analyses pre-diabetic/type 2 diabetic patients as well as those with sleepy OSA showed a greater response to CPAP. Regarding lipid metabolism, CPAP was associated with a mean total cholesterol reduction of 0.064mmol/L. In subgroup analyses, the benefit was higher in patients that showed more severe OSA and oxygen desaturations at the baseline sleep study as well as in younger and obese subjects. Neither glycated haemoglobin nor triglycerides, HDL- and LDL-cholesterol were reduced by CPAP. CONCLUSION: CPAP treatment may improve insulin sensitivity and total cholesterol levels in OSA patients but with low effect size. Our results suggest that CPAP does not substantially improve metabolic derangements in an unselected OSA population, but the effect may be higher in specific subgroups of OSA patients.


Insulin Resistance , Sleep Apnea, Obstructive , Humans , Glucose , Continuous Positive Airway Pressure , Randomized Controlled Trials as Topic , Triglycerides , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/complications , Cholesterol
9.
Kidney Int Rep ; 8(4): 700-714, 2023 Apr.
Article En | MEDLINE | ID: mdl-37069983

There is an increasing number of people with diabetes on peritoneal dialysis (PD) worldwide. However, there is a lack of guidelines and clinical recommendations for managing glucose control in people with diabetes on PD. The aim of this review is to provide a summary of the relevant literature and highlight key clinical considerations with practical aspects in the management of diabetes in people undergoing PD. A formal systematic review was not conducted because of the lack of sufficient and suitable clinical studies. A literature search was performed using PubMed, MEDLINE, Central, Google Scholar and ClinicalTrials.gov., from 1980 through February 2022. The search was limited to publications in English. This narrative review and related guidance have been developed jointly by diabetologists and nephrologists, who reviewed all available current global evidence regarding the management of diabetes in people on PD.We focus on the importance of individualized care for people with diabetes on PD, the burden of hypoglycemia, glycemic variability in the context of PD and treatment choices for optimizing glucose control. In this review, we have summarized the clinical considerations to guide and inform clinicians providing care for people with diabetes on PD.

10.
Diabetes Care ; 46(5): 1091-1097, 2023 05 01.
Article En | MEDLINE | ID: mdl-37062044

OBJECTIVE: There is limited information on the effect of ethnicity on the development of referable sight-threatening diabetic retinopathy (STDR) in people with type 1 diabetes. This study describes the risk factors for STDR in a diverse cohort of people with type 1 diabetes attending a regional diabetes eye screening service. RESEARCH DESIGN AND METHODS: Clinical and digital retinal imaging data from 1,876 people with type 1 diabetes (50% women, 72.1% Caucasian, 17.3% African Caribbean, 2.9% Asian, and 7.6% other) with no retinopathy at baseline, attending surveillance eye screening were reviewed. Referable STDR was defined as the presence of any moderate to severe nonproliferative or preproliferative diabetic retinopathy or proliferative diabetic retinopathy or maculopathy in either eye as per U.K. National Diabetic Eye Screening criteria. Median follow-up was 6 years. RESULTS: The median (interquartile range) age of the cohort was 29 (21, 41) years. Of the cohort of 1,876 people, 359 (19%) developed STDR. People who developed STDR had higher baseline HbA1c, raised systolic blood pressure (SBP), longer diabetes duration, and were more often of African Caribbean origin (24% vs. 15.6%; P < 0.05 for all). In multivariable Cox regression analyses, African Caribbean ethnicity (hazard ratio [HR] 1.39, 95% CI 1.09-1.78, P = 0.009), baseline SBP (HR 1.01, 95% CI 1.00-1.01, P = 0.033), and baseline HbA1c (HR 1.01, 95% CI 1.00-1.01, P = 0.0001) emerged as independent risk factors for STDR. CONCLUSIONS: We observed that people with type 1 diabetes of African Caribbean ethnicity are at significantly greater risk of STDR. Further research is required to understand the mechanisms that explain this novel observation.


Diabetes Mellitus, Type 1 , Diabetic Retinopathy , Humans , Female , Male , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetic Retinopathy/diagnosis , Glycated Hemoglobin , Ethnicity , Risk Factors
11.
Am Heart J ; 261: 1-9, 2023 07.
Article En | MEDLINE | ID: mdl-36934979

BACKGROUND: Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). METHODS: We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n = 19, placebo n = 26). RESULTS: Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. CONCLUSIONS: The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.


Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Humans , Male , Vitamin D , Calcitriol/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Vitamins/therapeutic use , Ergocalciferols/therapeutic use , Parathyroid Hormone/therapeutic use , Fibrosis , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/complications
12.
Diabet Med ; 40(4): e15027, 2023 04.
Article En | MEDLINE | ID: mdl-36524709

Diabetes is the commonest cause of end-stage kidney disease in many parts of the world, and many people on dialysis programmes live with diabetes. Such people are vulnerable to complications from their diabetes, and their care may be fragmented due to the many specialists involved. This updated guidance from the Joint British Diabetes Societies aims to review and update the 2016 guidance, with particular emphasis on glycaemic monitoring in the light of recent advances in this area. In addition, the guidance covers clinical issues related to the management of diabetes in people on peritoneal dialysis, along with acute complications such as hypoglycaemia and ketoacidosis, and chronic complications such as foot and eye disease.


Diabetes Mellitus , Hypoglycemia , Kidney Failure, Chronic , Adult , Humans , Renal Dialysis , Societies, Medical
13.
Bone ; 166: 116581, 2023 01.
Article En | MEDLINE | ID: mdl-36216304

People with diabetes and chronic kidney disease (CKD) are predisposed to bone mineral disorders and increased fracture risk. There is limited data on the effect of calcitriol on bone turnover markers (BTMs) in people with type 2 diabetes (T2DM) and stage 3 CKD. In a pre-specified secondary endpoint analysis of a 48-week randomized placebo controlled double-blind trial, we studied the effects of oral calcitriol 0.25 µg once daily on circulating BTMs that included osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTXI), procollagen type I N-propeptide (PINP) and fibroblast growth factor-23 (FGF-23). Inclusion criteria were people with T2DM with stable stage 3 CKD stage and intact parathyroid hormone (iPTH) >30 pg/ml. In total, 127 people [calcitriol (n = 64), placebo (n = 63)] were eligible for analyses. Baseline median (interquartile range) age of the cohort was 67 (60.5-70) years, iPTH (median range) 73.9 (55, 105) pg/ml and eGFR 40 (33, 48.5) ml/min. Calcitriol treatments resulted in a significant fall in iPTH, CTX, PINP and OCN levels and rise FGF-23, with mean (95 % confidence interval) between group differences in iPTH [-27.8 pg/ml; 95 % CI (-42.3 to -13.2); p < 0.001], FGF-23 [30.6 pg/ml; 95 % CI (14.8 to 46.3); p < 0.001], CTX [0.12 µg/l; 95 % CI (-0.19 to -0.06); (p < 0.001) and OCN [-4.03 ng/ml; 95 % CI (-7.8 to -0.27); p = 0.036]. Similarly we observed with calcitriol, as between treatment percentage change, a reduction of -38 % for iPTH, -34 % for CTX, and -28 % for OCN levels respectively (p < 0.05 for all). In people with T2DM and stage 3 CKD, calcitriol reduces the levels of CTX, OCN, PINP and iPTH. Further studies are needed to assess the clinical significance of our findings and the related long term impact on bone health.


Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Aged , Humans , Biomarkers , Bone Remodeling , Calcitriol/therapeutic use , Calcitriol/pharmacology , Collagen Type I , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Osteocalcin/pharmacology , Parathyroid Hormone/pharmacology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Vitamin D/pharmacology , Middle Aged
14.
Br J Clin Pharmacol ; 89(1): 279-289, 2023 01.
Article En | MEDLINE | ID: mdl-35942813

AIMS: Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD. METHODS: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible. RESULTS: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (-0.58 to 1.05) m/s, P = .57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of -27.8 (-42.3 to -13.2) pg/mL, P < .001. CONCLUSION: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.


Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Vascular Stiffness , Humans , Male , Female , Calcitriol/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Pulse Wave Analysis , Renal Insufficiency, Chronic/complications , Vitamin D
15.
Trends Endocrinol Metab ; 34(1): 1-4, 2023 01.
Article En | MEDLINE | ID: mdl-36357309

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were first used as antidiabetic agents that lower the blood glucose levels by promoting glycosuria. In recent years, randomised clinical trials have demonstrated that SGLT2i reduce cardiovascular-renal events and all-cause mortality in people with and without diabetes. The cardio-renal benefits observed are independent of glucose lowering effect and multiple mechanisms have been proposed for these results. SGLT2i can exert anti-ageing effects on the vasculature and other body organs through several signalling pathways including the activation of the nuclear factor erythroid-2-related factor 2 and the induction of antioxidant enzymes. We speculate that the pro-longevity effects of the SGLT2i are mediated by soluble Klotho, an anti-ageing kidney-derived hormone and an emerging therapeutic target for cardio-renal diseases.


Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/metabolism , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic use , Glucose , Sodium/therapeutic use
16.
Front Cardiovasc Med ; 9: 992327, 2022.
Article En | MEDLINE | ID: mdl-36247425

Objective: The mechanisms that explain the cardio-renal benefits of sodium glucose co-transporter 2 (SGLT-2) inhibitors are unknown. The effect of SGLT-2 inhibitors on arterial aging, measured by Aortic Pulse Wave Velocity (Ao-PWV) and Soluble Klotho (s-Klotho), a circulating anti-aging biomarker of arterial health are also unclear. Design/Setting: A 24-week single center randomized controlled trial (registry number/ EudraCT Number: 2013-004042-42) comparing Dapagliflozin and Ramipril (D+R) versus Ramipril (R) on the primary endpoint of urine albumin excretion rate (AER) and pre-specified secondary endpoints of Ao-PWV and biomarkers of arterial aging [s-Klotho and Fibroblast Growth Factor 23 (FGF-23)]. People with type 2 diabetes who had estimated glomerular filtration rate (eGFR) > 60 ml/min and residual microalbuminuria on maximum tolerated renin angiotensin system (RAS) inhibition were included in this study. Results: In total, 33 participants (male 73%) were randomized to either D+R (n = 17) or R (n = 16) arms. After 24 weeks of treatment, Ao-PWV (mean ± SD) did not change significantly from baseline D +R [9.06 ± 1.91 m/s to 9.13 ± 2.03 m/s], and R [9.88 ± 2.12 m/s to 10.0 ± 1.84 m/s]. AER fell significantly by 43.5% (95% CI: -57.36%, -29.56%; p < 0.01) in people in the D+ R arm only. We do not observe any significant changes in FGF-23 or s-Klotho. HbA1c and Angiotensin 1-7 fell significantly only in D + R arm. Conclusions: The combination of Dapagliflozin and Ramipril had no effects on Ao-PWV and s-Klotho which are biomarkers of arterial aging and cardio-renal risk. Our data suggest that the early cardio-renal benefits observed with SGLT-2 inhibitors are unlikely to be related to an improvement in arterial aging.

17.
Diabetes Care ; 45(9): 2095-2102, 2022 09 01.
Article En | MEDLINE | ID: mdl-36044663

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.


Diabetes Mellitus, Type 1 , Renal Insufficiency, Chronic , Albuminuria/complications , Caribbean Region , Diabetes Mellitus, Type 1/complications , Disease Progression , Ethnicity , Female , Glomerular Filtration Rate , Humans , Kidney , Male , Renal Insufficiency, Chronic/complications , Risk Factors
18.
Diabetes Care ; 45(10): 2456-2460, 2022 10 01.
Article En | MEDLINE | ID: mdl-36006615

OBJECTIVE: We tested the hypothesis that impaired awareness of hypoglycemia (IAH) is independently associated with symptoms of anxiety and depression in type 1 diabetes. RESEARCH DESIGN AND METHODS: In this cross-sectional observational study in 950 adults with type 1 diabetes, associations were examined using multiple regression models, adjusting for sociodemographic and clinical characteristics. RESULTS: Prevalence for probable anxiety, depression, and IAH were 9.4%, 9.8%, and 22.6%, respectively. When included in separate regression models, both depression and anxiety were independently associated with an increased odds of IAH and robust to adjustment (odds ratio 3.64 [95% CI 2.19-6.04] and 2.46 [1.46-4.14], respectively). Further analysis demonstrated a dose-response relationship between increased severity of probable mental disorder and increased odds of having IAH (P < 0.001). CONCLUSIONS: The robust independent relationship between probable anxiety and depression with IAH demonstrates the need for routine psychological assessment and management of people with type 1 diabetes and IAH.


Diabetes Mellitus, Type 1 , Hypoglycemia , Adult , Anxiety/epidemiology , Awareness , Cross-Sectional Studies , Depression/epidemiology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/psychology , Humans , Hypoglycemia/diagnosis
19.
Kidney Int Rep ; 7(4): 681-687, 2022 Apr.
Article En | MEDLINE | ID: mdl-35497783

Diabetic kidney disease (DKD) accounts for >40% cases of chronic kidney disease (CKD) globally. Hypertension is a major risk factor for progression of DKD and the high incidence of cardiovascular disease and mortality in these people. Meticulous management of hypertension is therefore crucial to slow down the progression of DKD and reduce cardiovascular risk. Randomized controlled trial evidence differs in type 1 and type 2 diabetes and in different stages of DKD in terms of target blood pressure (BP). Renin-angiotensin blocking agents reduce progression of DKD and cardiovascular events in both type 1 and type 2 diabetes, albeit differently according to the stage of CKD. There is emerging evidence for the benefit of sodium glucose cotransporter 2, nonsteroidal selective mineralocorticoid antagonists, and endothelin-A receptor antagonists in slowing progression and reducing cardiovascular events in DKD. This UK guideline, developed jointly by diabetologists and nephrologists, has reviewed all available current evidence regarding the management of hypertension in DKD to produce a set of comprehensive individualized recommendations for BP control and the use of antihypertensive agents according to age, type of diabetes, and stage of CKD (https://ukkidney.org/sites/renal.org/files/Management-of-hypertension-and-RAAS-blockade-in-adults-with-DKD.pdf). A succinct summary of the guideline, including an infographic, is presented here.

20.
Int J Endocrinol ; 2022: 8030765, 2022.
Article En | MEDLINE | ID: mdl-35256883

Background: Uncontrolled hyperglycaemia before and during hospitalisation is a risk factor for adverse outcomes in people with diabetes and SARS-CoV-2 infection. Insulin often at high doses is frequently required to manage hyperglycaemia associated with SARS-CoV-2 infection during hospitalisation. However, there is limited information on the clinical features and sequelae of people with type 2 diabetes (T2DM) not previously on insulin that require insulin as a new treatment when hospitalised with SARS-CoV-2 infection. Aims: To describe the clinical features and insulin treatment sequelae of 113 people with T2DM that required insulin as a new treatment when hospitalised with SARS-CoV-2 infection. Methods: A single-centre study of 113 people with T2DM who were not on insulin before their admission for SARS-CoV-2 infection. The primary aim of our study was to identify clinical and biochemical features that were associated with the need for insulin as a new treatment in people with known T2DM not on insulin treatment at the time of hospitalisation for SARS-CoV-2 infection. We also describe changes in insulin requirements at time of discharge from hospital and 6 weeks later during the first wave of SARS-CoV-2 infection (April-March 2020) in the UK. Clinical, biochemical, and anthropometric data were collected from electronic health records. Results: We observed that of 113 people with T2DM, 35% (n = 39) needed insulin as a new treatment during their hospitalisation for SARS-CoV-2 infection. People requiring insulin were younger, had a higher preadmission HbA1c, were more frequently on oral medication for diabetes before the admission, and were more likely to be obese (body mass index ≥30 kg/m2), with p ≤ 0.001 for all. In multivariable logistic regression analyses, we observed that younger age and higher HbA1c before admission were independently associated with needing insulin, with one-year increase in age associated with decreased odds of needing insulin initiation (OR 0.91, 95% CI 0.83-0.99), and increasing preadmission HbA1c by 1 mmol/mol associated with an increased odds of insulin initiation (OR 1.05, 95% CI 1.002-1.11) (p < 0.05 for both). Of the 39 people with T2DM who required insulin as a new treatment, 28% remained on insulin at the time of discharge with their insulin dose falling from 1.26 U/kg within the first 7 days of admission to 0.39 U/kg at discharge. At 6 weeks after discharge, 24% of people remained on insulin. Conclusion: More than one-third of people with T2DM not previously treated with insulin required new insulin treatment when hospitalised with SARS-CoV-2 infection, and of this group, 24% remained on insulin at 6 weeks after discharge. This study highlights the important variations of insulin requirements in people with T2DM new to insulin and the importance of a dedicated team for patient education and close follow-up.

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