Impact of blinded retrospective continuous glucose monitoring on clinical decision making and glycemic control in persons with type 2 diabetes on insulin therapy.

BACKGROUND AND AIMS: Blinded retrospective continuous glucose monitoring (rCGM) provides detailed information about real-life glycaemic profile. In persons with type 2 diabetes without adequate glycaemic control, the structured introduction of rCGM may be beneficial to sustain improvements in diabetes management. METHODS AND RESULTS: 102 individuals with insulin-treated type 2 diabetes, age less than 66 years old and HbA1c >7.5%, were recruited. Participants performed a 7-day blinded rCGM (iPro2) every four months for one year. Biochemical, anthropometric, and rCGM data was collected. Participants' and healthcare professionals' perceptions were assessed. 90 participants completed the protocol. HbA1c was 9.1 ± 0.1% one year prior to enrolment and 9.4 ± 0.1% at enrolment (p < 0.01). With the rCGM-based intervention, a decrease in HbA1c was achieved at 4 months (8.4 ± 0.1%, p < 0.0001), and 12 months (8.1 ± 0.1%, p < 0.0001). A significant increase in time-in-range was observed (50.8 ± 2.4 at baseline vs 61.5 ± 2.2% at 12 months, for 70-180 mg/dL, p < 0.001), with no difference in exposure time to hypoglycaemia. After 12 months, there was an increase in self-reported diabetes treatment satisfaction (p < 0.05). CONCLUSION: In persons with type 2 diabetes and poor metabolic control, specific data from blinded rCGM informed therapeutic changes and referral to targeted education consultations on nutrition and insulin administration technique. Therapeutic changes were made more frequently and targeted to changes in medication dose, timing, and/or type, as well as to lifestyle. Together, these brought significant improvements in clinical outcomes, effective shared decision-making, and satisfaction with treatment. REGISTRATION NUMBER: NCT04141111.

Review of methods for detecting glycemic disorders.

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity.

Prevalence, awareness, treatment and control of diabetes in Portugal: Results from the first National Health examination Survey (INSEF 2015).

AIMS: Diabetes Mellitus is a major public health threat worldwide and continues to increase in numbers and significance. Estimates of diabetes prevalence, awareness, treatment and control are essential to effectively monitor its trends, plan and evaluate interventions. METHODS: We conducted a nationwide health examination survey in the population residing in Portugal aged between 25 and 74 years old in 2015. It consisted in a cross sectional prevalence study which included the measurement of HbA1c, a physical examination and a general health interview of a probabilistic sample of 4911 individuals (Authorization n°9348/2010 of the National Committee for Data Protection). RESULTS: The overall prevalence of diabetes was 9.9% (95%CI: 8.4; 11.5). It was higher in males than in females (12.1% vs 7.8%). Diabetes was more prevalent among individuals of lower education and without any professional activity. The majority of persons with diabetes was aware of their condition (87.1%) and was taking antidiabetic medication (79.7%). Of these, 63.2% had glycated hemoglobin levels lower than 7.0% (53 mmol/mol), but the majority failed to comply with the LDL and blood pressure recommended clinical targets (71.9% and 59.0%). Similarly, the prevalence of prediabetes was 16%, higher among women than men (17.5% vs 14.4%). CONCLUSION: The prevalence of diabetes and prediabetes remains higher than the global and European estimates, although there is increasing awareness of this disorder.

HbA1c, Fructosamine, and Glycated Albumin in the Detection of Dysglycaemic Conditions.

Glycated haemoglobin (HbA1c) is currently the gold standard for glucose monitoring in patients with diabetes, and has been increasingly adopted as a criteria for diabetes diagnosis. However, conditions that determine alterations in haemoglobin metabolism can interfere with the reliability of HbA1c measurements. Glycated albumin and fructosamine (total glycated serum proteins) are alternative markers of glycaemia, which have been recognised to provide additional information to HbA1c or to provide a reliable measure when HbA1c is observed not to be dependable. Additionally, while HbA1c monitors the exposure to circulating glycaemia in the previous 3 months, glycated albumin and fructosamine represent exposure for a shorter period, which may be beneficial to monitor rapid metabolic alterations or changes in diabetes treatment. The present review further discusses the relative value of HbA1c, glycated albumin, and fructosamine, in prediabetes and diabetes diagnosis, evaluation of glucose variability, and complications risk prediction. Also, a novel molecular role for albumin is presented by which glycated albumin contributes to glucose intolerance development and thus to progression to diabetes, besides the role of glycated albumin as a pro-atherogenic factor.

Loss of postprandial insulin sensitization during aging.

With aging, there is a decrease in parasympathetic nervous activity. Since the hepatic parasympathetic nerves (HPNs) are essential to the disposal of nutrients, through the hepatic insulin sensitizing substance (HISS), we tested the hypothesis that aging leads to a lowering of postprandial glucose disposal by a decrease of the HISS-dependent component of insulin action. Insulin sensitivity was quantified in fed or fasted, male and female Wistar rats (from 6 to 52 weeks), using a euglycemic clamp. The HISS-dependent component was quantified by administration of the muscarinic antagonist atropine. Total insulin action decreased gradually up to 52 weeks of age: The HISS-independent component of insulin action decreased until 9 weeks of age and remained unchanged thereafter; the HISS-dependent component decreased from 9 weeks of age throughout aging. The continuous decrease of HISS action, uncovered by blocking the HPN, is the key phenomenon for the gradual decrease of insulin sensitivity with aging.

Insulin resistance in two animal models of obesity: A comparison of HISS-dependent and HISS-independent insulin action in high-fat diet-fed and Zucker rats.

Normal postprandial insulin sensitivity depends on the action of the hepatic insulin sensitizing substance (HISS), which requires hepatic parasympathetic nerve activation. Since HISS action is impaired in several pathological models, including the genetically-modified obese Zucker rat (OZR), we compared the HISS-dependent and HISS-independent components of insulin action between the OZR model, and the high-fat diet (HFD)-fed rats. We hypothesize that both models present an impaired HISS action, accounting for the decrease in insulin sensitivity. Male Sprague-Dawley rats fed a HFD for 1 week (n = 5) and OZR (n = 5) were used as obese models. Standard diet-fed (STD, n = 5) and lean Zucker rats (LZR, n = 6) were the HFD and OZR non-obese controls, respectively. Rats were 9-weeks-old when tested. Insulin sensitivity was measured in the fed state, before and after atropine blockade of HISS release), using the Rapid Insulin Sensitivity Test (RIST, mg glucose/kg bw). HISS-dependent action was the difference between control and post-atropine RISTs. HISS action was impaired in both the obese groups (HFD vs STD: 40.1 +/- 5.0 vs 117.0 +/- 3.8 mg glucose/kg bw, p < 0.001; OZR vs LZR: 34.4 +/- 12.8 vs 115.9 +/- 19.4 mg glucose/kg bw, p < 0.01), whereas the HISS-independent component (post-atropine RIST), i.e., insulin action per se, was decreased only in the OZR (OZR vs LZR: 39.3 +/- 3.5 vs 173.3 +/- 20.5 mg glucose/kg bw, p < 0.001). According to our data, the insulin resistance mechanisms are different in the two obesity models studied: in the HFD-fed rats, only the HISS-dependent component is impaired, whereas in the OZR both components of nsulin action are equally impaired.

Defective hepatic nitric oxide action results in HISS-dependent insulin resistance in spontaneously hypertensive rats.

Peripheral insulin sensitivity is dependent on the action of Hepatic Insulin Sensitizing Substance (HISS), in which hepatic NO (HNO) plays an important role. Insulin resistance has been associated with hypertension. NO action is known to be impaired in Spontaneously Hypertensive Rat (SHR) hypertension models. We tested the hypothesis that the HNO pathway is compromised in SHR, resulting in HISS-dependent insulin resistance. Wistar rats (Wis) were the normotensive controls. Insulin sensitivity was evaluated through the Rapid Insulin Sensitivity Test (RIST), a modified euglycemic clamp. A clamp was performed in basal state (control RIST), followed by ipv administration of the NO synthase (NOS) competitive antagonist L-NMMA (0.73 mg/kg) and a RIST post L-NMMA. HISS-dependent insulin sensitivity was assessed by subtracting the RIST post-L-NMMA from the control RIST and is represented as the resultant insulin sensitivity inhibition. In SHR ipv L-NMMA induced 26+/-5% insulin sensitivity inhibition (187.5+/-15.3 mg glucose/kg, n=6; P<0.05), whereas in Wis, ipv L-NMMA induced 53.8+/-5.9% insulin sensitivity inhibition (138.2+/-14.7 mg glucose/kg, n=6, P<0.05), significantly higher than in SHR (P<0.01). Our results suggest that functional HNO is essential to achieve maximal insulin sensitivity and that HNO action is compromised in hypertension, resulting in HISS-dependent insulin resistance.