Determining the optimal fasting glucose target for patients with type 2 diabetes: Results of the multicentre,open-label,randomized-controlled FPG GOAL trial

The optimal fasting blood glucose (FBG) target of achieving HbA1c less than 7.0% in type 2 diabetes (T2D) patients remains controversial. This open-label trial randomized (1:3:3) 947 adults with uncontrolled T2D (HbA1c >7% to ≤10.5%) who were using one to three oral antidiabetic drugs to achieve an FBG target of 3.9 < FBG ≤5.6 mmol/L (Group 1), 3.9 < FBG ≤6.1 mmol/L (Group 2) or of 3.9 < FBG ≤7.0 mmol/L (Group 3). Targets were achieved using a pre-defined insulin glargine 100 U/mL titration scheme. The primary endpoint was proportion of patients achieving HbA1c <7.0% at 24 weeks. At 24 weeks, 44.4%, 46.1% and 37.7% of patients achieved HbA1c <7.0% in Groups 1, 2 and 3, respectively (P = 0.017; Group 2 vs Group 3). Alert hypoglycaemia (glucose ≤3.9 mmol/L) was significantly more frequent in Group 1 than in Group 3 (38.9 vs 23.3%; P < 0.001) but was not in Group 2 vs Group 3 (27.5% vs 23.3%; P = 0.177). Clinically important hypoglycaemia (glucose ≤3.0 mmol/L) was reported in 4.8%, 2.0% and 3.8% of patients in Groups 1, 2 and 3, respectively. In conclusion, the optimal FBG target for most Chinese patients with T2D appears to be 3.9-6.1 mmol/L.     

The relationship between blood glycosylated haemoglobin and home capillary blood glucose levels in diabetics

Summary Serial capillary blood glucose levels from insulin treated patients were recorded over 24 hour periods at fortnightly intervals for three months. Total glycosylated haemoglobin as % of HbA was measured at the end of this period by the Flückiger method, and % HbA₁ by column chromatography. There were highly significant correlations between mean blood glucose levels over the three months and % HbA₁ (r=0.93, 95% confidence limits 0.84–0.98), and with total glycosylated haemoglobin (r=0.88, 95% confidence limits 0.75–0.94). There was also a good correlation between results obtained by the two methods (r=0.81, p<0.0001). There were less strong correlations between % HbA₁ and blood glucose levels during each of the three months before the estimation, with percentage of glucose levels greater than 10 mmol/l and with mean fasting blood glucose. These data support the hypothesis that % HbA₁ and total glycosylated haemoglobin are satisfactory measurements of short term diabetic control.     

Validation of an algorithm combining haemoglobin A1c and fasting plasma glucose for diagnosis of diabetes mellitus in UK and Australian populations

Aim To determine whether glycated haemoglobin (HbA_1c) can be used in combination with fasting plasma glucose (FPG) for the diagnosis of diabetes in patients with impaired fasting glucose (IFG) and in a broader spectrum of patients. Methods An algorithm was derived from oral glucose tolerance test (OGTT) capillary samples in 500 consecutive UK patients with IFG by World Health Organization criteria. It was validated in a further 500 UK patients and, with venous specimens, in 1175 unselected Australian patients. Results The derivation cohort was aged 61 years (50–69 years) (median IQ range) with 52% male and 12% South Asian. Diabetes Control and Complications Trial‐aligned HbA_1c was 6.2% (5.8–6.6%) (reference interval < 6.0%) and FPG 6.7 mmol/l (6.3–7.2 mmol/l). FPG was in the diabetes range in 36% of patients, with an OGTT identifying a further 12% with diabetes. The derived algorithm, (HbA_1c ≥ 6.0% with FPG < 7.0 mmol/l) identified those patients requiring an OGTT to diagnose diabetes. When applied to the UK validation cohort, sensitivity was 97% and specificity 100%. The algorithm was equally effective in the unselected group, aged 59 years (49–68 years) and 54% male, with sensitivity 93% and specificity 100%. HbA_1c was 6.0% (5.6–6.6%) and FPG 6.0 mmol/l (5.3–6.8 mmol/l), with 26% having IFG. Use of the algorithm would reduce the number of OGTTs performed in the UK validation cohort by 33% and by 66% in the Australian patients studied. Conclusions Use of this algorithm would simplify procedures for diagnosis of diabetes and could also be used for monitoring pre‐diabetes. Validation is now required in other populations and patient groups.     

Glycosylated haemoglobin and steady-state mean blood glucose concentration in type 1 (insulin-dependent) diabetes

Summary Since glucose control and glycosylated haemoglobin varies asyncroneously, we have studied the steady-state relationship between these two factors. In Type 1 (insulin-dependent) diabetic patients with a constant haemoglobin A_1c during the preceding 2 years, 15 ambulatory blood glucose profiles during a 5-week period showed a constant glucose level and provided a precise estimate of the mean blood glucose concentration. In addition, we studied 15 non-diabetic subjects who provided three glucose profiles and had one haemoglobin A_1c determination performed. A good correlation was found for a curvilinear relationship (haemoglobin A_1c=2.07 x mean blood glucose^0.596, r=0.98). This close relationship indicates that glycosylated haemoglobin is a valuable, but not very sensitive, index of glucose control.     

Genetic selection for high and low fasting blood glucose levels in mice. I. Fasting blood glucose levels,glucose tolerance and isolated tissue studies

Summary Swiss-Hauschka mice have been selected for high (HG) and low (LG) fasting blood glucose (FBG) levels for four generations. All matings were brother to sister. Differences in mean FBG levels have remained relatively constant (20 to 30 mg%) between the two lines since initiation of selection (p<0.001). Body weights have declined more rapidly with inbreeding in the LG line as compared to the HG line through F₃, but no further decline was noted in the F₄ generation. Fasting serum immunoreactive insulin (IRI) levels were variable and mean levels for the two lines did not differ significantly. A comparison of glucose tolerance data between F₃ HG and LG line animals showed generally higher mean glucose levels in the HG line in both fasted and randomfed states. The mean delta glucose levels during the test, however, were nearly identical in both lines. A dietary influence on glucose tolerance was shown. Severalin vitro tissue studies revealed no significant differences in hepatic glycogen and pancreatic insulin content between HG and LG line animals. Isolated tissue sensitivity to insulin appeared indistinguishable between the lines; however, hepatic gluconeogenesis and retinal glucose-6-¹⁴C oxidation rates in HG line mice may be enhanced.Supported in part by U.S.P.H.S. Grants AM-11959, AM-09748, 1-FO3-AM-30777, and AM-05077, and the Upjohn Company, Kalamazoo, Michigan.     

红细胞体积分布宽度与糖代谢异常/糖耐量异常和糖尿病相关

目的探讨红细胞体积分布宽度（RDW）与2型糖尿病（T2DM）、空腹血糖受损／葡萄糖耐量异常（IFG／IGT）的相互关系。方法对152例在我院定期进行健康体检或治疗的患者,依据血糖情况分为3组,其中T2DM组42例,IFG／IGT组38例,正常对照（NGT）组72例,采取空腹血,采用全自动血液分析仪测定RDW、血红蛋白,多功能血生化自动分析仪测定血总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血肌酐、血尿素氮和空腹血糖,同时统计高血压、冠心病的发病率并分析其关系。结果RDW在T2DM组、IFG／IGT组和NGT组之间比较具有统计学差异,其中T2DM组和NGT组、IFG／IGT组比较,差异均有统计学意义（P〈0．05或P〈0．01）,IFG／IGT组与NGT组比较差异无统计学意义（P〉0．05）。多因素直线回归分析显示空腹血糖（P〈0．01）和高密度脂蛋白胆固醇（P〈0．05）是RDW的独立危险因子。结论T2DM患者RDW升高,RDW的变化与空腹血糖水平相关。     

The relative merits of haemoglobin A1c and fasting plasma glucose as first-line diagnostic tests for diabetes mellitus in non-pregnant subjects

HbA_1c was measured by high-performance ion-exchange chromatography in 401 non-pregnant patients undergoing oral glucose tolerance tests (OGTT). All those with HbA_1c>6.2 % (reference range 3.8–5.5 %) had diabetic OGTT (sensitivity 41 %, specificity 100 %). Although a fasting plasma glucose (FPG) cut-off ≥7.0 mmol l⁻¹, as recommended by the American Diabetes Association (ADA), had greater sensitivity (78 %), false positives (12 %) limited its usefulness, so more diagnostic confidence could be placed in a positive HbA_1c. In agreement with the ADA, we found FPG gave only slightly lower diabetes prevalence than the OGTT, but this masked a significant number of individual discrepancies (false positives and negatives) cancelling out each other. The new ADA category of impaired fasting glucose did not correlate well with impaired glucose tolerance. HbA_1c is insufficiently sensitive as a direct substitute for the OGTT. A third of subjects diabetic on OGTT had normal HbA_1c values, so it cannot exclude diabetes as currently defined, but HbA_1c screening could make sufficient positive diagnoses to reduce our non-pregnant OGTTs by one-fifth. If a ‘risk threshold’ for diabetic complications could be applied to HbA_1c, it could replace the OGTT as a more pragmatic diagnostic/prognostic test. © 1998 John Wiley & Sons, Ltd.     

The potential of cinnamon to reduce blood glucose levels in patients with type 2 diabetes and insulin resistance

Aim: Cinnamon has a long history as an antidiabetic spice, but trials involving cinnamon supplementation have produced contrasting results. The aim of this review was to examine the results of randomized controlled clinical trials of cinnamon and evaluate the therapeutic potential amongst patients with diabetes and insulin-resistant patients, particularly the ability to reduce blood glucose levels and inhibit protein glycation.
Methods: A systematic electronic literature search using the medical subject headings 'cinnamon' and 'blood glucose' was carried out to include randomized, placebo-controlled in vivo clinical trials using Cinnamomum verum or Cinnamomum cassia conducted between January 2003 and July 2008.
Results: Five type 2 diabetic and three non-diabetic studies (total N = 311) were eligible. Two of the diabetic studies illustrated significant fasting blood glucose (FBG) reductions of 18–29% and 10.3% (p < 0.05), supported by one non-diabetic trial reporting an 8.4% FBG reduction (p < 0.01) vs. placebo, and another illustrating significant reductions in glucose response using oral glucose tolerance tests (p < 0.05). Three diabetic studies reported no significant results.
Conclusions: Whilst definitive conclusions cannot be drawn regarding the use of cinnamon as an antidiabetic therapy, it does possess antihyperglycaemic properties and potential to reduce postprandial blood glucose levels. Further research is required to confirm a possible correlation between baseline FBG and blood glucose reduction and to assess the potential to reduce pathogenic diabetic complications with cinnamon supplementation.     

The relationship between self-monitoring of blood glucose results and glycated haemoglobin in type 2 diabetes: the fremantle diabetes study

The benefits of self-monitoring of blood glucose (SMBG) in type 2 diabetes remain contentious. If SMBG data do not accurately reflect HbA_1c, attempts to modify lifestyle/pharmacotherapy will be ineffective. We aimed to determine how well SMBG correlates with HbA_1c and fasting serum glucose (FSG). Community-based type 2 patients using SMBG provided their highest and lowest pre- and post-prandial glucose results in the week before detailed assessment. The ability of average pre- and post-prandial SMBG to predict HbA_1c > 7.0% was determined by linear regression and receiver operating characteristic (ROC) analyses. Of 1286 patients with known SMBG status, 70% reported using SMBG. Pre-prandial SMBG data were obtained from 554 participants and post-prandial SMBG data from 418. The mean SMBG result and HbA_1c correlated significantly (pre-prandial r_s = 0.55, post-prandial r_s = 0.47; P < 0.001). Areas under the ROC curve (95% confidence limits) were 0.78 (0.74-0.83) and 0.74 (0.69-0.78) for pre- and post-prandial SMBG (P < 0.04). The optimal cut-point was 6.5 mmol/L for pre-prandial SMBG (sensitivity 79.3%, specificity 64.4%). Mean pre-prandial SMBG results correlated with FSG (r_s = 0.64, P < 0.001) but were on average 1.4 mmol/L lower, consistent with known whole blood vs. plasma differences. Since SMBG values reflect prevailing glycaemia, refinements in their interpretation and application may improve SMBG effectiveness.     

Stabilization of postprandial blood glucose fluctuations by addition of glucagon like polypeptide‐analog administration to intensive insulin therapy

Aims/Introduction

The nature of the action of concomitant liraglutide to stabilize postprandial blood glucose level (PBG) in patients on intensive insulin therapy with unstable PBG remains unclear. The aim was to identify the nature of liraglutide''s actions to stabilize PBGs.

Materials and Methods

The study participants consisted of 20 diabetes patients showing unstable PBGs after dinner despite undergoing intensive insulin therapy. The dose of bolus insulin was reduced by three units for each meal, and 0.9 mg/day of liraglutide was added and used in combination. We evaluated the participants'' data after the first evaluation (immediately before using liraglutide in combination) and the second evaluation (16 weeks after starting concomitant therapy). PBGs after dinner were measured every day for a period of 28 days immediately before carrying out both evaluations. The mean value of the 28 sets of blood glucose data and their standard deviation (SD) values were established as PBGs after dinner, as well as the SD for each participant. The changes in the mean values of the 20 participants, as well as their SD between before and after concomitant therapy, were evaluated.

Results

The mean value of PBGs (12.0 ± 1.0 to 10.1 ± 0.9 mmol/L) and SD values (5.1 ± 0.7–3.5 ± 0.8) after dinner both declined. A multiple regression analysis showed that the combined use of liraglutide was a significant independent variable of the SD values of PBGs after dinner.

Conclusion

The treatment of reducing the dose of insulin and using liraglutide in combination not only suppresses PBGs, but also stabilizes their blood glucose fluctuations.     

A comparison of the predictive power for overall blood glucose control of a 'good' fasting level in type 2 diabetic patients on diet alone or with oral agents.

The European NIDDM Policy Group classifies both fasting and post-prandial blood glucose concentrations into 'good', 'acceptable', and 'poor' categories. The aim of the present study was to evaluate whether a 'good' fasting blood glucose concentration in Type 2 diabetic patients on diet or diet + oral hypoglycaemic agents is able to predict 'good' blood glucose values throughout the day, and therefore to discover whether or not it is necessary to perform blood glucose profiles in Type 2 diabetic patients when their fasting value is 'good'. Capillary blood glucose profiles (n = 417) were measured in 287 Type 2 diabetic patients, on diet alone (279 profiles), or on diet + tablets (138 profiles). We observed that 66% of profiles on diet and 44% of profiles on diet + tablets had only 'good' blood glucose concentrations (p less than 0.001). Eleven percent of profiles on diet and 30% of profiles on diet + tablets included 'poor' blood glucose concentrations (p less than 0.001). Despite matched fasting blood glucose concentrations (diet 5.69 +/- 0.04 (+/- SE) vs tablets 5.75 +/- 0.05 mmol l-1), levels were higher in the diet + tablet treated patients at all later time-points (p less than 0.01-0.001). HbA1c was significantly higher in tablet-treated patients than in patients on diet alone (6.6 +/- 0.1 vs 5.9 +/- 0.1%, p less than 0.001), and correlated with the mean blood glucose concentration (r = 0.43, p less than 0.001) but not with the fasting glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic glucose production during intraperitoneal and intravenous closed-loop insulin regulation of blood glucose in Type 1 (insulin-dependent) diabetic patients

Summary Intraperitoneal infusion of insulin should be more physiological than intravenous insulin since part of the insulin is directed toward the portal vein, which allows the liver to retain its major role in glucose homeostasis. The regulation of hepatic glucose production during the intraperitoneal and intravenous infusions of insulin were compared in eight Type 1 (insulin-dependent), C-peptide-deficient diabetic patients. Primed, continuous infusions of [6,6-²H] glucose were given in the postabsorptive state and during continuous infusion of unlabelled glucose at 1.5 and 4 mg/kg· min, while normoglycaemia was maintained by closed-loop intraperitoneal and intravenous insulin delivery. During all three periods, plasma glucose concentrations remained near normal (variations 3.8–6.1%). The insulin infusion rates required for normal plasma glucose concentrations were essentially the same for the intravenous and intraperitoneal routes in all cases, although the variations were greater with intraperitoneal insulin. Plasma free-insulin levels were only slightly, non-significantly lower with intraperitoneal infusion than with intravenous infusion. Hepatic glucose production was significantly lower with intraperitoneal insulin during all three conditions: basal: 1.71±0.14, i.p. vs 2.37±0.26 mg/kg · min, i.v.; 1.5 mg/kg · min glucose infusion: 0.49±0.23, i.p. vs 0.88±0.18 mg/kg · min, i.v.; 4 mg/kg · min glucose infusion: 0.31±0.10, i.p. vs 0.56±0.12 mg/kg · min, i.v. These results, obtained with steady-state conditions for plasma glucose, isotopic plasma glucose enrichments and unlabelled glucose infusion rates, suggest that better control of hepatic glucose production leading to normoglycaemia was achieved with the intraperitoneal infusion.     

The co‐formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia,independent of baseline glycated haemoglobin levels,disease duration or body mass index: A pooled meta‐analysis of phase III studies in patients with type 2 diabetes

Aims

To investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes.

Materials and methods

This was a post hoc pooled analysis of 5 phase III randomized, 26‐week, open‐label, treat‐to‐target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories.

Results

We conducted a meta‐analysis of 5 clinical trials: NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End‐of‐trial results were broadly consistent, with differences between IDegAsp and comparators observed in phase III trials. HbA1c results were similar for IDegAsp and the comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI) and category groups (number ranges). Significantly lower FPG level was observed with IDegAsp vs comparators in all baseline characteristic and most category groups (excluding FPG <5.5 mmol/L). Significantly lower insulin doses were observed with IDegAsp vs comparators in all baseline characteristic and half of the category groups, and significantly lower rates of confirmed and nocturnal confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline variable and category groups.

Conclusions

IDegAsp retains a consistent safety and efficacy profile in patients with different baseline characteristics.     

Lower mean blood glucose during short‐term intensive insulin therapy is associated with long‐term glycemic remission in patients with newly diagnosed type 2 diabetes: Evidence‐based recommendations for standardization

Aims/Introduction

Optimal glycemic targets during short‐term intensive insulin therapy in patients with newly diagnosed type 2 diabetes are not standardized. The present study was carried out to determine the optimal glycemic targets during therapy by analyzing the impacts of glucose levels on therapeutic outcomes.

Materials and Methods

A total of 95 individuals with newly diagnosed type 2 diabetes were enrolled. Short‐term intensive insulin therapy was carried out using an insulin pump to achieve and maintain glycemic targets (fasting blood glucose ≤6.0 mmol/L, 2‐h postprandial blood glucose ≤7.8 mmol/L) for 14 days, with daily eight‐point capillary blood glucose profiles recorded. Patients were followed up for 1 year after discharge.

Results

In most participants, the mean blood glucose and glycemic excursion parameters during the therapy were controlled within the normal range. Mean blood glucose was independently associated with amelioration of acute insulin response (r = ?0.25, P = 0.015) and 1‐year remission (odds ratio 0.12, 95% confidence interval 0.034–0.426), but negatively associated with more level 1 hypoglycemia (r = ?0.34, P = 0.001), although major hypoglycemia was rare. Among mean blood glucose tertiles, patients in the middle (68.7%) and lower (75.0%) tertiles had a higher 1‐year remission rate compared with the upper tertile (32.3%, both P < 0.001), whereas only the middle tertile did not have increased hypoglycemia compared with the upper tertile (8.1 ± 5.4 vs 7.2 ± 3.9 events/person, P = 0.48).

Conclusions

Stricter glycemic control during short‐term intensive insulin therapy produced more remission despite self‐manageable hypoglycemia. Based on glycemic parameters in the middle mean tertile, we propose new glycemic targets that are approximately 0.4 mmol/L lower than current the targets, as long‐term benefit outweighs short‐term risks.

     

Relationship between hypoglycemic symptoms and blood glucose levels due to self-monitoring in summer camp for diabetic children in Japan

In a summer camp for 47 diabetic children in Kinki district, Japan, in 1984, the relationship between hypoglycemic symptoms and blood glucose levels by self-monitoring was analyzed. During the 7-day camp, self-monitoring of blood glucose (SMBG) was carried out 599 times in total, 12.7 times per camper. SMBG due to hypoglycemic complaints amounted to 371. 154 measurements out of 371 indicated blood glucose levels under 80 mg/dl, but 78 monitorings were found to be over 200 mg/dl. Fatigue or weakness were the most frequent hypoglycemic symptoms, as was hunger sensation, each reaching approximately 40% in frequency. In most complaints of tremor, the blood glucose level was critically low. Prompt measurement of blood glucose is indeed necessary to properly treat diabetic children with 'hypoglycemic' symptoms.