Sodium-glucose cotransporter-2 inhibitors (SGLT2) in frail or older people with type 2 diabetes and heart failure: a systematic review and meta-analysis.

OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model. RESULTS: We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis. CONCLUSIONS: In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.

Contrast-enhanced ultrasound for the evaluation of symptomatic and asymptomatic carotid plaques: A systematic review and meta-analysis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a promising imaging modality for the assessment of plaque vulnerability. We aimed to systematically review and meta-analyze the ability of CEUS parameters to differentiate between symptomatic and asymptomatic carotid plaques and to assess its reproducibility. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for studies that potentially evaluated carotid plaques using CEUS. From the initial 2870 searches, 11 relevant publications comprising a total of 821 carotid plaques were reviewed. Data on CEUS parameters including quantitative and semi-quantitative parameters were extracted and analyzed. RESULTS: The overall analysis showed significantly higher CEUS parameters in symptomatic carotid plaques compared to asymptomatic carotid plaques (standardised mean difference (SMD) .95, 95% confidence interval (CI) .56-1.27, p < .01). Intra and inter-observer reproducibility of quantitative CEUS parameters were excellent (intra-observer, r = .95, 95% CI .87-1; inter-observer, r = .93, 95% CI .80-.1). Semi-quantitative CEUS parameters showed good intra-observer reliability and moderate inter-observer reliability (intra-observer, r = .77, 95% CI .64-.89; inter-observer, r = .75, 95% CI .61-.89). Heterogeneity among studies compared CEUS parameters in symptomatic and asymptomatic plaques and studies assessed inter-observer reproducibility, and significant biases in studies assessing CEUS reproducibility were present. CONCLUSION: CEUS is a useful vascular imaging method to differentiate between symptomatic and asymptomatic carotid plaques with moderate to excellent reproducibility. Quantitative CEUS analysis appeared to be more sensitive and reliable in assessing carotid plaques than semi-quantitative parameters. Further longitudinal prospective trials evaluating carotid plaque in asymptomatic population using CEUS to determine plaque characteristics that can become symptomatic are required.

Associations between Zinc Deficiency, Taste Changes, and Salivary Flow Rates following Gastric Bypass and Sleeve Gastrectomy Surgeries.

Background: The prevalence of taste change (hypogeusia) and its association with zinc deficiency is unclear due to differences in methods of assessment. We investigate the prevalence of hypogeusia using mixed methods and link it with changes in zinc levels following mini gastric bypass (MGB) and sleeve gastrectomy (SG). Methods: This was a prospective observational study of MGB (N = 18) and SG (N = 25). Hypogeusia was evaluated by using a validated questionnaire and by taste strips procedure along with serum zinc levels and salivary flow rate measurements. Results: The mean age was 40.0 ± 9.7 years; 60.5% were female. By using a questionnaire, MGB patients experienced greater hypogeusia than SG at 3 months (72.0% vs 36.0%; (p=0.03)), but not at 6 months (56.0% vs 45.0%; (p=0.74)), respectively. Using taste strips, at 6 months, more MGB patients experienced hypogeusia compared with SG (44.0% vs 11.0%; p=0.03). Zinc level was reduced following MGB at 6 months (85.6 ± 16.9 µgm/dl vs 67.5 ± 9.2 µgm/dl; (P=0.004)) but was increased at 6 months following SG (76.9 ± 11.4 vs 84.9 ± 21.7 µgm/dl). Reduction in the rate of salivary flow was observed in 66.0% and 72.0% of MGB and SG patients, respectively, at 3 months and in 53.0% and 70.0% at 6 months. Conclusion: Taste change is more prevalent following MGB compared with SG, especially at 6 months postoperation which parallel with changes in zinc levels. More than half of all patients who had undergone bariatric surgery (BS) had low to very low salivary flow rates during the follow-up. This study suggests an association between low zinc levels and reduced salivary flow with hypogeusia following BS.

Is 3D ultrasound reliable for the evaluation of carotid disease? A systematic review and meta-analysis.

AIM: Studies assessing the use of 3D ultrasound (3DUS) for the evaluation of carotid disease reported varying views among observers about its reliability vis-à-vis 2DUS or angiography; ratings provided ranged from poor to excellent. Thisstudy aims to systematically review and analyze the reliability of 3DUS for the evaluation of carotid disease. MATERIALS AND METHODS: The PubMed database was searched for studies that evaluated carotid disease (i.e. plaque measurements and characteristics and degree of stenosis) using 3DUS. RESULTS: Sixteen studies comprising a total of 918 stenosed carotids were reviewed and meta-analyzed. Data on intra- and inter-observer reproducibility and inter-method agreement (i.e. 3DUS vs 2D and 3DUS vs angiography) were analyzed. Overall analysis showed excellent intra- and inter-observer reproducibility (intraobserver: correlation coefficient r=0.88, 95% confidence intervals (CI) 0.84-0.92; intra-observer: r=0.91, 95% CI 0.87-0.95). The analysis also showed excellent agreement between 3DUS and 2DUS (r=0.89, 95% CI 0.83-0.95) and between 3DUS and angiography (r=0.73, 95% CI 0.44-0.1). CONCLUSION: 3DUS has excellent intra- and inter-observer reproducibility and excellent agreement with 2DUS and angiography for the evaluation of carotid disease. Further studies assessing the reliability ofcarotid plaque characteristics using 3DUS in symptomatic and asymptomatic patients are required.

Diagnosis of parotid gland tumours with Contrast-Enhanced Ultrasound: a systematic review and meta-analysis.

AIM: Contrast-enhanced ultrasound (CEUS) appears to be a promising application for the diagnosis of parotid gland tumours. We aimed to systematically review and meta-analyse the ability of CEUS in distinguishing benign from malignant parotid gland tumours. MATERIAL AND METHODS: PubMed was searched for relevant studies. Data on area under time intensity curve (AUC) in arbitrary unit (AU), and mean transit time (MTT) in seconds (sec) were analysed using the Cochrane Review Manager Software. RESULTS: Nine studies met the eligibility criteria comprising a total number of 498 parotid gland tumours (benign, number (n)=423; malignant, n=75). Descriptive evaluation of parotid gland tumours following CEUS administration showed overlap characteristics in benign and malignancies. Two publications assessed AUC and MTT in 72 and 60 parotid gland tumours, respectively. AUC was significantly lower in benign compared to malignant tumours following contrast administration (AUC, mean difference (MD) -266.77 AU, 95% confidence intervals (CI) -433.22, -100.33, p=0.002). No significant different in MTT between benign and malignant tumours (p=0.12). Heterogeneity was statistically significant in AUC (p=0.04) and MTT (p<0.00001). CONCLUSION: Descriptive evaluation of parotid gland tumours showed overlap CEUS characteristics. Perfusion related CEUS parameters analysis is promising in differentiating benign parotid tumours from malignancies.

Is carotid artery atherosclerosis associated with poor cognitive function assessed using the Mini-Mental State Examination? A systematic review and meta-analysis.

OBJECTIVES: To determine associations between carotid atherosclerosis assessed by ultrasound and the Mini-Mental State Examination (MMSE), a measure of global cognitive function. DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE and EMBASE databases were searched up to 1 May 2020 to identify studies assessed the associations between asymptomatic carotid atherosclerosis and the MMSE. Studies reporting OR for associations between carotid plaque or intima-media thickness (cIMT) and dichotomised MMSE were meta-analysed. Publication bias of included studies was assessed. RESULTS: A total of 31 of 378 reviewed articles met the inclusion criteria; together they included 27 738 participants (age 35-95 years). Fifteen studies reported some evidence of a positive association between measures of atherosclerosis and poorer cognitive performance in either cross-sectional or longitudinal studies. The remaining 16 studies found no evidence of an association. Seven cross-sectional studies provided data suitable for meta-analysis. Meta-analysis of three studies that assessed carotid plaque (n=3549) showed an association between the presence of plaque and impaired MMSE with pooled estimate for the OR (95% CI) being 2.72 (0.85 to 4.59). An association between cIMT and impaired MMSE was reported in six studies (n=4443) with a pooled estimate for the OR (95% CI) being 1.13 (1.04 to 1.22). Heterogeneity across studies was moderate to small (carotid plaque with MMSE, I2=40.9%; cIMT with MMSE, I2=4.9%). There was evidence of publication bias for carotid plaque studies (p=0.02), but not cIMT studies (p=0.2). CONCLUSIONS: There is some, limited cross-sectional evidence indicating an association between cIMT and poorer global cognitive function assessed with MMSE. Estimates of the association between plaques and poor cognition are too imprecise to draw firm conclusions and evidence from studies of longitudinal associations between carotid atherosclerosis and MMSE is limited. PROSPERO REGISTRATION NUMBER: CRD42021240077.

The metabolic and liver-related outcomes of bariatric surgery in adult patients with insulin-treated type 2 diabetes and nonalcoholic fatty liver disease at high risk of liver fibrosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease, with a prevalence estimated to between 20% and 30% of the general population and approximately 70% of stage 2 obese people with type 2 diabetes (T2D) with normal liver enzymes. OBJECTIVES: To investigate the metabolic and liver-related outcomes of bariatric surgery among patients with insulin-treated T2D and NAFLD who are at high risk of liver fibrosis. SETTING: More than 600 locations within the United Kingdom. METHODS: The study comprises a retrospective cohort comparison of patients with NAFLD and a fibrosis 4 (Fib-4) score > 1.45 who received a bariatric intervention versus comparable patients who received no bariatric intervention. Metabolic outcomes (glycated hemoglobin [HbA1C] level, weight, body mass index [BMI], and Fib-4 score) and composite liver-related outcomes (cirrhosis, portal hypertension, liver failure, and hepatoma) were compared between groups over a period of 5 years. The outcomes were adjusted for baseline and time-varying covariates. RESULTS: The study sample included 4108 patients, 45 of whom underwent bariatric surgery. The mean age at baseline was 62.4 ± 12.4 years; 43.8% of patients were female; the mean weight was 89.5 ± 20.8 kg; the mean BMI was 31.7 ± 7.6 kg/m2; and the mean HbA1C level was 68.4 ± 16.7 mmol/mol. In addition, the median Fib-4 score was 2.3 (interquartile range, 1.7-4.2). During the 5 years during which follow-up outcomes were recorded, the weight and BMI reductions were significantly lowered compared with baseline in the bariatric surgery group. Similarly, the HbA1C levels were lower in the bariatric surgery group, with statistically significant differences observed in the first and second postintervention years (bariatric surgery versus non-bariatric surgery patient levels at 1 year, 63.1 mmol/mol versus 68.1 mmol/mol, respectively [P = .042], and at 2 years, 62.7 mmol/mol versus 68.1 mmol/mol, respectively [P = .028]). No significant difference was observed between groups in the proportion of patients with liver fibrosis or the likelihood of developing composite liver disease during the follow-up period (bariatric surgery group, 8.9%; non-bariatric surgery group, 4.7%; X2 = 1.75; P = .18). CONCLUSION: Bariatric surgery amongst patients with insulin-treated T2D with NAFLD who were at high risk of liver fibrosis was associated with significant improvements in metabolic outcomes. No significant adverse effects were observed with regards to liver-related outcomes.

Clinical cost evaluation and health benefits of post-bariatric intervention for patients with type 2 diabetes living in the UK.

To assess associated healthcare costs and risk of developing obesity-related comorbidities among patients with type 2 diabetes with severe obesity and receiving insulin treatment, following bariatric surgery (BS). A retrospective cohort study was conducted from a UK electronic primary care database. Propensity score matching (1:1) was performed for BS with non-BS cohort. Follow-up was over 5 years (694 person-years), comparing drug utilization with clinical cost differences, such as visits to General practitioners (GPs), hospitalization, and laboratory use. Cox proportional regression was used to compute differences in the risk of obesity-related comorbidities and chi-square analysis to explore differences in insulin independency and diabetes remission proportions during follow-up. Eighty patients who received BS were matched to 80 non-BS (N = 160). The baseline mean age was 48.3 years (SD: 12.9) (61% female), and body mass index was 39.3 kg/m2 (SD: 9.3). During follow-up, antidiabetic drug cost was significantly lower in the BS group than in the non-BS (median cost/person [£]: 527.77 [interquartile range (IQR): 1196.11] vs. 1564.13 [IQR: 1576.01]; p < 0.001). Overall, aggregate cost analysis showed a significant total healthcare cost reduction in the BS group (median cost/person [£]: 1597.96 [IQR: 2631.84] vs. 2440.12 [IQR: 2242.95]; p = 0.050). BS significantly protected against obesity-related comorbidities compared with the non-BS (adjusted hazard ratio: 0.56; 95% confidence interval: 0.32-0.96; p = 0.036) and increased insulin independency throughout all follow-up points: at year 5: 48.1% versus 28.9%; p = 0.044, respectively. While BS shows evidence of cost efficiency, cost saving was not identified. The efficiency is evident by the protective effect against crude obesity-related comorbidities associated with increased insulin independency.

Diuretics and risk of lower extremity amputation amongst patients with insulin-treated type 2 diabetes - exploring the mechanism of possible sodium glucose co-transporter 2 inhibitor induced risk of lower extremity amputations.

AIMS AND BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor has been linked to an increased risk of lower extremity amputation (LEA) in patients with Type 2 Diabetes (T2D) and is known to induce volume depletion through osmotic diuresis. We investigated the potential association between diuretics use and the LEA risk in insulin-treated T2D patients. METHODS AND MATERIALS: A retrospective cohort study was conducted on 10,320 insulin-treated T2D patients within the UK population. Cox proportional hazard models were utilised to estimate LEA hazard ratios. Amputation risk was compared between a propensity score-matched cohort of diuretics users versus non-users over a 20-year period. RESULTS: Among 10,320 subjects, 6454 (52.3%) were on diuretics. In the full cohort, diuretic-treated patients had significantly higher risk of LEA than the non-diuretic individuals (HR: 1.89; 95%CI: 1.34-2.68). When adjusting for possible confounding effects, a 2.3-fold higher risk of amputation was observed (aHR: 2.45; 95%CI: 1.63-3.69). In the matched cohort (n = 580), this association is marginally significant (HR: 3.33; 95%CI: 1.17-18.9; p = .029). CONCLUSION: While diuretic use appeared to be associated with an increased risk of LEA among insulin-treated T2D patients, this association is marginally significant after controlling for confounding factors by cohort matching. These results suggest that volume depletion may be a factor in increasing the risk of LEA amongst high-risk T2D patients, but the strength of this association is weak when adjusted for all other risk factors. Thus, patient selection is crucial when determining the safe use of agents that induce volume depletion in high risk patients with T2D.

Effect of Bariatric Surgery on Diagnosed Chronic Kidney Disease and Cardiovascular Events in Patients with Insulin-treated Type 2 Diabetes: a Retrospective Cohort Study from a Large UK Primary Care Database.

AIMS: To compare the effect of bariatric surgery on renal, chronic kidney disease (CKD) and cardiovascular (CV) outcomes among obese patients with insulin-treated type 2 diabetes (T2D) with and without microalbuminuria (i.e., uACR > 3.0 mg/mmol). METHODS: A retrospective cohort study was conducted among 11,125 active patients with T2D from The Health Improvement Network (THIN) database. Propensity score matching (up to 1:6 ratio) was used to identify patients who underwent bariatric surgery (N = 131) with a non-bariatric cohort (N = 579). Follow-up was undertaken for 10 years (6487 person-years) to compare differences in risk of cardiovascular events and in renal outcomes. RESULTS: For the matched cohort at baseline: mean age 52 ± 13 years (60% female); weight 116 ± 25 kg, body mass index (BMI) 41 ± 9kg/m2, estimated glomerular filtration rate (eGFR); 70.4 ± 20 mL/min/1.73 m2, and median albumin-creatinine ratio (uACR) 2.0 mg/mmol (interquartile range (IQR): 0.9-5.2 mg/mmol). Bariatric surgery was associated with a 54% reduction in developing CKD compared to their matched non-bariatric cohort (adjusted hazard ratio [aHR]: 0.46; 95%CI: 0.24-0.85, P = 0.02). Among patients with microalbuminuria at baseline, bariatric surgery was protective against CKD (aHR: 0.42, 95%CI: 0.18-0.99, P = 0.050). eGFR was significantly increased from baseline favouring the bariatric group during 75% of the follow-up time (calculated mean difference between groups: 4.1 mL/min/1.73 m2; P < 0.05), especially at 5-year point (74.2 vs 67.8 mL/min/1.73 m2; P < 0.001). However, no significant change was observed with non-fatal CVD episodes (aHR: 0.36, 95%CI: 0.11-1.13, P = 0.079). Albumin levels were significantly reduced throughout the 2 years following the surgery (3.9 vs 4.1 g/dL, P < 0.001). uACR and total protein levels had little or no statistical association to the intervention. CONCLUSION: Bariatric surgery may protect patients with diabetes with or without microalbuminuria against the risk of CKD and with a modest protective effect on non-fatal CVD risk. Bariatric surgery is also associated with improvements in overall renal outcomes such as eGFR.

Clinical characteristics and patient treatment satisfaction with Humalog U-200 in patients with type 2 diabetes mellitus: an observational study.

Background: There are limited data on the real-world evidence of Humalog 200 units/ml KwikPen (U-200) insulin. We assessed the use of U-200 insulin in UK routine clinical practice to provide information on clinical characteristics, treatment satisfaction and short-term clinical outcomes. Methods: Nine patients with type 2 diabetes who initiated U-200 in secondary care and a further 12 identified from primary care electronic database were enrolled. A treatment satisfaction questionnaire was administered to the 19 secondary care patients. Follow-up data on clinical parameters were collected at 3 and 6 months following initial U-200 insulin administration and the data were used to assess changes in clinical outcomes from baseline. Results: Secondary care patients had a mean age 60 ± 11 years, mean HbA1c of 8.6% ± 1.3% and a mean BMI of 39.7 ± 5.3 kg/m2 at baseline. Primary care database patients had a mean age 57 ± 13 years, mean HbA1c 10.3% ± 1.7 and a mean BMI 42.3 ± 3.8 kg/m2. The nine participants' responses to the questionnaire suggested a high preference for U-200 over a previous mealtime insulin pen (PMIP). On average, the patients agreed that U-200 was quicker to inject, had a better controlled home blood glucose reading and less discomfort at the injection site compared to a PMIP. Patients were willing to continue with their U-200 treatment. No significant HbA1c reduction was observed at 3 months in the secondary care group (-0.5%), but marked significant reduction in HbA1c was seen at 3 months in the primary care dataset to (-2.8%; p < .0004). There was also some suggestion of weight loss in both the secondary and primary care groups. Conclusion: Humalog U-200 insulin users were comprised mainly of older patients with diabetes complications and high HbA1c levels at the time of U-200 initiation. Overall, U-200 improved patients' satisfaction with diabetes treatment and short-term metabolic outcomes.

Effect of Bariatric Surgery on Cardiovascular Events and Metabolic Outcomes in Obese Patients with Insulin-Treated Type 2 Diabetes: a Retrospective Cohort Study.

AIMS: To compare non-fatal cardiovascular (CV) events and metabolic outcomes, among obese patients with insulin-treated type 2 diabetes who underwent bariatric surgery compared with a propensity-matched non-bariatric cohort. METHODS: A retrospective cohort study was conducted among 11,125 active patients with type 2 diabetes from The Health Improvement Network (THIN) database. Propensity score matching (up to 1:6 ratio) was used to identify patients who underwent bariatric surgery (N = 131) with a non-bariatric cohort (N = 579). Follow-up was undertaken for 10 years (9686 person-years) to compare differences in metabolic outcomes and CV risk events that included the following: acute myocardial infarction (AMI), stroke, coronary heart disease (CHD), heart failure (HF) and peripheral artery disease (PAD). Cox proportional regression was used to compute the outcomes between groups. RESULTS: The mean age was 52 (SD 13) years (60% female); the baseline weight and BMI were 116 (SD 25) kg and 41 (SD 9) kg/m2, respectively. Significant reductions in weight and BMI were observed in bariatric group during 10 years of follow-up. Bariatric surgery had a significant cardioprotective effect by reducing the risk of non-fatal CHD (adjusted hazard ratio [aHR] 0.29, 95% CI 0.16-0.52, p < 0.001) and PAD events (aHR 0.31, 95% CI 0.11-0.89, p = 0.03). However, the surgery had no significant effect on AMI (aHR 0.98, p = 0.95), stroke (HR 0.87, p = 0.76) and HF (HR 0.89, p = 0.73) risks. Bariatric surgery had favourable effects on insulin independence, HbA1c and BP. CONCLUSION: Among obese insulin-treated patients with type 2 diabetes, bariatric surgery is associated with significant reductions in non-fatal CHD and PAD events, lower body weight, HbA1c, BP and a greater likelihood of insulin independency during 10 years of follow-up.

Tier 3 specialist weight management service and pre-bariatric multicomponent weight management programmes for adults with obesity living in the UK: A systematic review.

BACKGROUND: NHS England has recommended a multidisciplinary weight management services (MWMS-Tier 3 services) for patients requiring specialized management of obesity, including bariatric surgery, but clinical and measurable health-related outcomes from these services remains fragmented. We therefore undertook a systematic review to explore the evidence base of effect on body weight loss and comorbidities outcomes of Tier 3 or UK pre-bariatric MWMPs. METHODS: AMED, CINAHL, EMBASE, HMIC, MEDLINE, PsycINFO, PubMed, HDAS search and Google Scholar were searched from January 2000 to September 2017 in a free-text fashion and crossed-references of included studies to identify potential illegibility. Inclusion criteria were as follows: (a) published Tier 3 original study abstracts/articles; (b) intervention studies with before and after data; (c) studies that included any sort of MWMPs conducted on British residents with obesity; and (d) studies included T2DM measurements in a MWMPs. RESULTS: In total, 19 studies met the inclusion criteria. The total number of participants analysed was N = 11,735. Baseline accumulative average BMI was calculated at 42.54 kg/m2, weight 117.88 kg and waist circumference 126.9 cm. And at 6 months, 40.73 kg/m2, 112.17 kg and 120.3 cm, respectively. Secondary outcome variables were as improved with reduction in HbA1c, fasting blood sugars, insulin usage and blood pressure. Physical activity increased at 3 months then declined after 6 months with no significant changes in cholesterol levels. CONCLUSION: Tier 3 and MWMPs have a short to mid-ranged positive effect on obese patients (BMI ≥30 kg/m2) living in the UK regarding accumulated reduction in weight, glycaemic control, blood pressure and with subtle improvements in physical activity.