The effect of extend bar containing uncooked cornstarch on night-time glycemic excursion in subjects with type 2 diabetes

The objective of this study was to determine the effects of ingesting a snack bar containing uncooked cornstarch (Extend Bar, Clinical Products, Limited, Key Biscayne, FL) on nocturnal glycemic excursion in 28 adults (ages 22-78 years) with type 2 diabetes mellitus (mean HbAlc 8.21+/-1.28%). Thirteen subjects were treated with oral agents, eight with a combination of insulin and oral agents, and seven with insulin alone. Subjects ingested the study bar (Extend Bar, containing 30 g of total carbohydrate, including 5 g of uncooked cornstarch, 3 g protein, and 3 g fat) for three evenings followed by a placebo bar for 3 evenings (30 g of total carbohydrate, 3 g protein, and 3 g fat), or vice versa. Pre-snack before bedtime, midnight and before breakfast finger stick blood glucose levels were compared to determine the incidence of hypoglycemia (<60 mg/dl), hyperglycemia (>250 mg/dl), and to calculate any differences in the group's mean blood glucose levels when ingesting the study versus the placebo bar. There were no episodes of hypoglycemia or hyperglycemia. The mean blood glucose levels pre-snack at bedtime were nearly identical (Extend Bar value 117.5+/-45.6 mg/dl; placebo bar value 117.3+/-40.0 mg/dl; P=0.977), and lower at midnight and before breakfast on the Extend Bar nights compared to the placebo bar nights (Extend Bar, midnight value 127.9+/-31.0 mg/dl; placebo bar midnight value 148.2+/-32.1 mg/dl; P=0.0001; Extend Bar breakfast value 114.2+/-15.8 mg/dl; placebo bar breakfast value 158.49+/-30.3 mg/dl; P<0.0001). These data suggest that ingesting Extend Bar containing uncooked cornstarch as the nighttime snack may be an effective strategy to lesson the frequency of nocturnal and morning hyperglycemia in subjects with type 2 diabetes.     

Nocturnal hypoglycemia in type 1 diabetes: an assessment of preventive bedtime treatments

OBJECTIVE: We assessed four putative bedtime treatments in the prevention of nocturnal hypoglycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS: Plasma glucose concentrations were measured every 15 min from 2200 h through 0700 h in 21 patients with type 1 diabetes (mean +/- sd HbA(1C) = 7.1 +/- 1.0%) on five occasions with, in random sequence, bedtime (2200 h) administration of 1) no treatment, 2) a snack, 3) the snack plus the alpha-glucosidase inhibitor acarbose, 4) an uncooked cornstarch bar, or 5) the beta(2)-adrenergic agonist terbutaline. RESULTS: In the absence of a bedtime treatment, 27% of the measured nocturnal plasma glucose concentrations were less than 70 mg/dl (3.9 mmol/liter) in 12 patients; 16, 6, and 1% were less than 60, less than 50, and less than 40 mg/dl (3.3, 2.8, and 2.2 mmol/liter), respectively. Neither the snack (without or with acarbose) nor cornstarch raised the mean nadir nocturnal glucose concentration or reduced the number of low glucose levels or the number of patients with low levels. Terbutaline raised the mean nadir nocturnal glucose concentration (mean +/- se, 127 +/- 11 vs. 75 +/- 9 mg/dl; P < 0.001), eliminated glucose levels less than 50 mg/dl (P = 0.038), reduced levels less than 60 mg/dl (P = 0.005) to one, and reduced levels less than 70 mg/dl (P = 0.001) to five (four at 2215 h, one at 2230 h). However, it also raised glucose levels the following morning. CONCLUSIONS: Nocturnal hypoglycemia is common in aggressively treated type 1 diabetes. Bedtime administration of a conventional snack or of uncooked cornstarch does not prevent it. That of terbutaline prevents nocturnal hypoglycemia but causes hyperglycemia the following morning. The efficacy of a lower dose of terbutaline remains to be determined.     

Bedtime uncooked cornstarch supplement prevents nocturnal hypoglycaemia in intensively treated type 1 diabetes subjects

Abstract . Axelsen M, Wesslau C, Lönnroth P, Arvidsson Lenner R, Smith U (Sahlgrenska University Hospital, Göteborg University, Sweden). Bedtime uncooked cornstarch supplement prevents nocturnal hypoglycaemia in intensively treated IDDM subjects. J Intern Med 1999; 245 : 229–36. Objectives. The present study tests two interrelated hypotheses: (1) that bedtime ingestion of uncooked cornstarch exerts a lower and delayed nocturnal blood glucose peak compared with a conventional snack; (2) that bedtime carbohydrate supplement, administered as uncooked cornstarch, prevents nocturnal hypoglycaemia without altering metabolic control in intensively treated type 1 diabetes (IDDM) patients. Design  and subjects. The above hypotheses were tested separately (1) by pooling and analysing data from two overnight studies of comparable groups of patients with non-insulin dependent diabetes mellitus (NIDDM) (14 and 10 patients, respectively), and (2) by a double-blind, randomized 4-week cross-over study in 12 intensively treated IDDM patients. Setting. Sahlgrenska University Hospital, Göteborg, Sweden. Interventions. (1) Ingestion of uncooked cornstarch and wholemeal bread (0.6 g of carbohydrates kg^?1 body weight) and carbohydrate-free placebo at 22.00 h. (2) Intake of uncooked cornstarch (0.3 g kg^?1 body weight) and carbohydrate-free placebo at 23.00 h. Main outcome measures. (1) Nocturnal glucose and insulin levels; (2) frequency of self-estimated hypoglycaemia (blood glucose [BG] levels < 3.0 mmol L^?1) at 03.00 h, HbA_1c and fasting lipids. Results. Bedtime uncooked cornstarch ingestion led to a lower (2.9 ± 0.5 vs. 5.2 ± 0.6 m m , P = 0.01) and delayed (4.3 ± 0.6 vs. 2.0 ± 0.0 h, P < 0.01) BG peak, compared with a conventional snack, in NIDDM patients. Four weeks of bedtime uncooked cornstarch supplement, as compared with placebo, led to a 70% reduction in the frequency of self-estimated hypoglycaemia at 03.00 h (P < 0.05), without affecting HbA1c or fasting lipids in IDDM patients. Conclusions. Uncooked cornstarch, ingested at bedtime, mimicked the nocturnal glucose utilization profile following insulin replacement, with a peak in blood glucose after 4 h. In IDDM patients, bedtime uncooked cornstarch supplement diminished the number of self-estimated hypoglycaemic episodes, without adversely affecting HbA1c and lipid levels. Hence, bedtime uncooked cornstarch ingestion may be feasible to prevent a mid-nocturnal glycaemic decline following insulin replacement in IDDM and, based on the nocturnal blood glucose profile, may also be preferable compared with conventional snacks.     

Biochemical evidence for the requirement of continuous glucose therapy in young adults with type 1 glycogen storage disease

Summary To determine whether patients with GSD-1 need nocturnal glucose therapy after completing physical growth and development, studies were performed on two consecutive nights. On the first night uncooked cornstarch (UCS) was given at the calculated glucose production rate at 21:00 h and 02:00 h. On the second night UCS was given at 21:00 h but omitted at 02:00 h. Six GSD-1 patients, aged 17.2–20.9 years, previously treated with continuous glucose therapy were studied. Measurements were made of plasma glucose (PG), serum insulin, growth hormone, cortisol, plasma glucagon (n=4), and blood lactate at 30–60-min intervals. Serum uric acid, cholesterol, and triglycerides were measured at 21:00 h and 07:00 h, and serum FFA at 21:00 h, 02:00 h and 07:00 h on the first night and immediately before treatment for hypoglycaemia on the second night.For five hours after UCS at 21:00 h, mean PG, serum insulin and blood lactate concentrations were similar on the two nights. With UCS at 02:00 h, mean PG concentrations were 4.1 mmol/L from 02:00 to 07:00 h. Without UCS at 02:00 h, in all subjects PG concentrations fell to <2.5 mmol/L after 6.5–8.5 h and mean blood lactate concentration increased to 7.4±3.0 mmol/L.Young adults with GSD-1 developed hypoglycaemia and hyperlactataemia after a relatively brief period without exogenous glucose and, therefore, need to continue nocturnal glucose therapy to prevent fasting hypoglycaemia.     

Dynamic change in collateral flow associated with myocardial ischemia in humans

Background: This study sought to investigate how collateral flow changes during myocardial ischemia in patients. Methods: Myocardial contrast echocardiography (MCE) and rapid atrial pacing were performed in 20 patients with angiographically evidenced coronary collaterals from the right coronary artery (RCA) to the occluded left anterior descending coronary artery. Sonicated contrast medium was injected into the RCA before and immediately after atrial pacing to determine the peak background-subtracted contrast intensity (PI) in the collateral territory (PIA) and its ratio to PI in the control territory (PI ratio) as parameters of collateral blood flow. Lactate production in the coronary circulation during pacing was determined to assess myocardial ischemia in the collateral territory. Results: PIA showed a significant correlation with regional wall motion either before (r(squared)=−0.64, P<0.01) or after pacing (r(squared)=−0.65, P<0.01). Similarly, PI ratio was significantly correlated with regional wall motion either before (r(squared)=−0.54, P<0.05) or after pacing (r(squared)=−0.64, P<0.01). Rapid atrial pacing decreased both PIA and PI ratio significantly greater in patients with lactate production than in those without (PIA: −67±53 vs. −15±34%, P<0.05; PI ratio: −68±49 vs. −8.2±32%, P<0.05, respectively), while neither PIA nor PI ratio differ between the two groups of patients before pacing (PIA: 13.8±19. vs. 16.2±13.3U, P=0.75; PI ratio: 0.70±0.71 vs. 0.87±0.65, P=0.58, respectively). Conclusions: We concluded that (1) collateral flow determined by MCE was closely associated with regional cardiac function, and (2) not the amount of collateral flow at rest, but pacing-induced change of collateral flow seemed to be a determinant of regional ischemia in patients with coronary collaterals.     

Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73

The UK Prospective Diabetes Study (UKPDS) showed that a more intensive glucose control policy reduced risk of diabetic complications. As hypoglycemia is a barrier to achieving glycemic targets, we examined its occurrence and contributing factors in UKPDS patients randomized to and remaining for 6 years on diet, sulfonylurea, metformin (overweight subjects only), or insulin monotherapy from diagnosis of Type 2 diabetes. Self-reported hypoglycemic episodes were categorized as (1) transient, (2) temporarily incapacitated, (3) requiring third-party assistance, and (4) requiring medical attention, recording the most severe episode each quarter. Proportions of patients reporting at least one episode per year were calculated in relation to therapy, HbA_1c, and clinical characteristics. In 5063 patients aged 25–65 years, only 2.5% per year reported substantive hypoglycemia (Grades 2–4) and 0.55% major hypoglycemia (Grade 3 or 4). Hypoglycemia was more frequent in younger (4.0% <45 years vs. 2.2% ≥45 years), female (3.0% vs. 2.2% male), normal weight (3.6% body mass index <25 kg/m² vs. 1.9% ≥25 kg/m²), less hyperglycemic (5.2% HbA_1c <7% vs. 2.3% ≥7%), or islet autoantibody-positive patients (4.3% vs. 2.1% negative) (all P<.0001). More on basal insulin reported hypoglycemia (3.8% per year) than diet (0.1%), sulfonylurea (1.2%), or metformin (0.3%) therapy, but less than on basal and prandial insulin (5.3%) (all P<.0001). Low hypoglycemia rates seen during the first 6 years of intensive glucose lowering therapy in Type 2 diabetes are unlikely to have a major impact on attempts to achieve guideline glycemic targets when sulfonylurea, metformin, or insulin are used as monotherapy.     

Evaluating the Performance of a Novel Embedded Closed-loop System

The objective was to assess the reliability of a novel automated closed-loop glucose control system developed within the AP@home consortium in adults with type 1 diabetes. Eight adults with type 1 diabetes on insulin pump therapy (3 men; ages 40.5 ± 14.3 years; HbA1c 8.2 ± 0.8%) participated in an open-label, single-center, single-arm, 12-hour overnight study performed at the clinical research facility. A standardized evening meal (80 g CHO) accompanied by prandial insulin boluses were given at 19:00 followed by an optional snack of 15 g at 22:00 without insulin bolus. Automated closed-loop glucose control was started at 19:00 and continued until 07:00 the next day. Basal insulin delivery (Accu-Chek Spirit, Roche) was automatically adjusted by Cambridge model predictive control algorithm, running on a purpose-built embedded device, based on real-time continuous glucose monitor readings (Dexcom G4 Platinum). Closed-loop system was operational as intended over 99% of the time. Overnight plasma glucose levels (22:00 to 07:00) were within the target range (3.9 to 8.0 mmol/l) for 75.4% (37.5, 92.9) of the time without any time spent in hypoglycemia (<3.9 mmol/l). Mean overnight glucose was 7.8 ± 1.3 mmol/l. For the entire 12-hour closed-loop period (19:00 until 07:00) plasma glucose levels were within the target range (3.9 to 10.0 mmol/l) for 84.4% (63.3, 100) of time. There were no adverse events noted during the trial. We observed a high degree of reliability of the automated closed-loop system. The time spent in target glucose level overnight was comparable to results of previously published studies. Further developments to miniaturize the system for home studies are warranted.     

Glucose and insulin responses to intravenous glucose challenge in relatives of Nigerian patients with non-insulin-dependent diabetes mellitus

We analysed blood insulin and glucose concentrations before and during frequently sampled intravenous glucose tolerance tests (FSIGT) in 2 groups of Nigerian subjects: (A) Control group (n = 18), without a positive family history of diabetes mellitus, and (B) Experimental group (n = 16), comprising age-, sex- and body mass-matched first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM). In comparison with Group A subjects, those in Group B had: (i) higher fasting plasma glucose level (mean ± S.E.M., 4.1 ± 0.1 vs. 3.8 ± 0.11 mmol/l, P < 0.05); (ii) similar fasting serum insulin levels (6.7 ± 5.0 vs. 5.8 ± 5.6 mU/l, P = NS); (iii) lower mean incremental area under the first-phase (t = 0–10 min) post-glucose challenge insulin curve (376.9 ± 8.8 vs. 435.6 ± 5.6 mU/min l⁻¹, P < 0.05); (iv) increased incremental area under the second-phase (t = 10–182 min) post-glucose challenge insulin curve (432.9 ± 11.5 vs. 161.3 ± 8.7 mU/min l⁻¹, P < 0.05); (v) reduced K_G rate constant of glucose elimination (0.97 ± 0.12 vs. 1.41 ± 0.12%/min, P < 0.05). These results suggest that the subjects with a positive family history of NIDDM have a reduced beta-cell insulin secretory reserve (from reduced first-phase insulin response), tendency to rebound hyperinsulinemia during the latter phase of the insulin secretory response, a degree of tissue insulin insensitivity (as evident from high fasting plasma glucose despite similar insulin levels) and a diminished glucose disposal rate, in comparison with subjects without a family history of NIDDM. These features predict subsequent development of diabetes and suggest that as in Caucasians, first-degree relatives of Nigerian patients with NIDDM are at greater risk for future development of the disease.     

Post-exercise response of the systolic blood pressure in the diagnosis of coronary artery disease: comparison of two exercise methods

We studied 81 angiographically documented coronary artery disease patients and 28 with normal coronary arteries, having paired exercise tests (the Bruce treadmill protocol and the jogging in place test) in order to investigate the value of the ratio of recovery systolic blood pressure to peak exercise systolic blood pressure (postexercise pressure ratio) compared to the classic ST depression. The postexercise pressure ratio was significantly higher in patients with coronary artery disease than in patients with normal coronary arteries for each of the 2 exercise tests (P < 0.001 − P < 0.00001). On the contrary, we obtained significantly lower sensitivities for the pathologic (> ± 2 SD of patients with normal coronary arteries) values of the post-exercise pressure ratio than for the positive electrocardiographic outcome 30% vs 58% (P < 0.00002) and 37% vs 64% (P < 0.0001) as well as lower accuracies 48% vs 63% (P < 0.03) and 52% vs 71% (P < 0.005), respectively.

Thus, we proved that the classic ST depression has much more diagnostic value than the post-exercise pressure ratio and this result is independent of the exercise methodology. Consequently this ratio is not recommended to replace the electrocardiographic exercise criteria.     

Adrenoceptor antagonists, but not guanethidine, reduce glucopenia-induced glucagon secretion from perfused rat pancreas

This study was designed to investigate (1) whether norepinephrine is released in response to glucopenia in vitro, thereby stimulating glucagon secretion and, (2) the modulating effects of norepinephrine on insulin and glucagon secretion, using isolated perfused rat pancreas preparations. Simultaneous addition of the adrenergic receptor antagonists yohimbine, prazosin and propranolol, each at a concentration of 10⁻⁵ mol/l, significantly potentiated glucose-stimulated insulin secretion (6.23 ± 0.76 vs. 2.11 ± 0.72 (control) nmol/min, P < 0.01), and suppressed glucopenia-induced glucagon secretion (0.59 ± 0.10 vs. 1.34 ± 0.18 (control) ng/min, P < 0.05). Also, 10⁻⁵ mol/l yohimbine alone significantly potentiated glucose-stimulated insulin secretion (4.86 ± 0.50 nmol/min, P < 0.05). The norepinephrine release inhibitor, guanethidine, significantly inhibited tyramine-induced secretion of both norepinephrine (7.86 ± 0.77 vs. 49.7 ± 2.3 nmol/min, P < 0.01) and glucagon (0.31 ± 0.08 vs. 1.21 ± 0.15 ng/min, P < 0.01), but exerted no effects on glucopenia-induced secretion of either norepinephrine or glucagon. We conclude that these results further support the concept that the neurotransmitter norepinephrine is released in response to glucopenia in vitro, and modulates insulin and glucagon secretion. Our data do not, however, provide evidence indicating that glucopenia-induced glucagon secretion is mainly mediated by activation of sympathetic nerve terminals around the -cells in the isolated perfused rat pancreas.     

Benefit of uncooked cornstarch in the management of children with dumping syndrome fed exclusively by gastrostomy

Objective: Children with dumping syndrome fed exclusively by gastrostomy are difficult to manage because liquid diets are given directly into the antrum. The gastric contents are emptied rapidly into the small intestine, with consequent hyperglycemia followed by a delayed hypoglycemia and multiple, often debilitating, symptoms. Uncooked cornstarch is a complex carbohydrate that provides a slow and continuous glucose source and may delay gastric emptying. The objective of this study was to determine the efficacy of uncooked cornstarch in the treatment of these children.
Methods: The medical records of eight children with dumping syndrome fed exclusively by gastrostomy were reviewed. Dumping syndrome was diagnosed if there was consistent symptomatology, rapid gastric emptying, and abnormal glucose measurements after a glucose tolerance test. Enough uncooked cornstarch to match hepatic glucose production for 4 h was added to control hypoglycemia, and the feeding formula was modified to control hyperglycemia.
Results: All patients had debilitating symptoms. Weight z-score on admission was −2.31 ± 0.29. Glucose shifts were controlled in all. There was a significant difference between the maximum (221.3 ± 19.3 mg/dl vs 121.3 ± 6.9 mg/dl;   p < 0.008  ) and minimum serum glucose (47 ± 7.8 mg/dl vs 65.6 ± 4 mg/dl;   p < 0.04  ) before and after uncooked cornstarch. Weight increased from 11.87 ± 1.4 kg to 15.10 ± 2.3 kg (   p = 0.06  ). In seven patients, bolus feedings were successfully administered, and symptoms improved or resolved.
Conclusions: Uncooked cornstarch controlled the glucose shifts, resolved most of the symptoms, allowed bolus feedings, and enhanced weight gain in these children.     

Feasibility of overnight closed-loop control based on hourly blood glucose measurements

Introduction

Safe and effective closed-loop control (artificial pancreas) is the ultimate goal of insulin delivery. In this study, we examined the performance of a closed-loop control algorithm used for the overnight time period to safely achieve a narrow target range of blood glucose (BG) concentrations prior to breakfast. The primary goal was to compare the quality of algorithm control during repeated overnight experiments.

Materials and Methods

Twenty-three subjects with type 1 diabetes performed 2 overnight experiments on each of three visits at the study site, resulting in 138 overnight experiments. On the first evening, the subject’s insulin therapy was applied; on the second, the insulin was delivered by an algorithm based on subcutaneous continuous glucose measurements (including meal control) until midnight. Overnight closed-loop control was applied between midnight and 6 a.m. based on hourly venous BG measurements during the first and second nights.

Results

The number of BG values within the target range (90–150 mg/dl) increased from 52.9% (219 out of 414 measure-ments) during the first nights to 72.2% (299 out of 414 measurements) during the second nights (p < .001, χ²-test). The occurrence of hypoglycemia interventions was reduced from 14 oral glucose interventions, the latest occurring at 2:36 a.m. during the first nights, to 1 intervention occurring at 1:02 a.m. during the second nights (p < .001, χ²-test).

Conclusions

Overnight controller performance improved when optimized initial control was given; this was suggested by the better metabolic control during the second night. Adequate controller run-in time seems to be important for achieving good overnight control. In addition, the findings demonstrate that hourly BG data are sufficient for the closed-loop control algorithm tested to achieve appropriate glycemic control.     

Reduction of urinary albumin excretion by thromboxane synthetase inhibitor, OKY-046, through modulating renal prostaglandins in patients with diabetic nephropathy

We evaluated the effects of thromboxane synthetase inhibitor, OKY-046, on urinary albumin and prostaglandin (PG) excretion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM).

Urinary excretion of 6-keto-PGF₁ (a stable metabolite of PGI₂), TXB₂ (a stable metabolite of TXA₂) and PGE₂ in NIDDM patients was comparable with that in control subjects. However, the urinary 6-keto-PGF₁/TXB₂ ratio in NIDDM patients with both micro- and macroalbuminuria was significantly (P < 0.001) lower than that in the controls.

By a single administration of OKY-046 (40 mg, i.v.) to the diabetic patients, urinary TXB₂ excretion significantly (P < 0.05) decreased from 169.7 ± 23.9 to 140.2 ± 17.9 ng/gCr, but urinary 6-keto-PGF₁ and PGE₂ excretion did not change significantly. The urinary 6-keto-PGF₁/TXB₂ ratio thus significantly (P < 0.01) increased from 1.02 ± 0.13 to 1.73 ± 0.41 as associated with significant increments in urine volume (P < 0.05), urinary sodium excretion (P < 0.01) and creatinine clearance (P < 0.05).

Of 14 diabetic patients, 7 with macroalbuminuria (albumin index exceeding 100 mg/gCr) were orally given OKY-046 (600 mg/day) for 8 weeks. After this period, the urinary albumin index significantly (P < 0.05) decreased from 524.9 ± 149.6 to 317.6 ± 90.6 mg/gCr. Urinary PG excretion did not change significantly, although the urinary 6-keto-PGF₁/TXB₂ ratio significantly (P < 0.01) increased from 1.33 ± 0.16 to 2.42 ± 0.65 and decreased to 1.09 ± 0.15 (P < 0.01) following termination of this drug. Similarly, creatinine clearance significantly (P < 0.01) increased, from 56.3 ± 14.1 to 69.4 ± 15.1 ml/min. During the period of 8 weeks, no significant alteration occurred in systemic blood pressure or glycemic control.

In conclusion, OKY-046 has a beneficial effect on albuminuria in diabetic nephropathy by modulating altered renal PGs synthesis, which leads to a change in renal hemodynamics.     

A randomized clinical trial comparing breakfast and bedtime administration of insulin glargine in children and adolescents with type 1 diabetes

Background: Insulin glargine provides effective glycemic control when administered at bedtime in adults.Objective: This study aims to investigate whether insulin glargine is equally effective if administered in the morning or at bedtime in combination with preprandial anologue insulin.Methods: Twenty−eight patients that have been treated with an intensified insulin regimen for at least one year were randomized to insulin glargine injection at breakfast (06:00−09:00) (12 patients) or bedtime (21:00−24:00) (16 patients), plus meal−time anologue insulin in the two groups. Glucose data from each day were analyzed at four different times: between 9:00 and 21:00 (t1), between 21:00 and 24:00 (t2), between 24:00 and 04:00 (t3),04:00 and 09:00 (t4) by the Minimed continuous glucose monitoring system. Results: Baseline characteristics were similar in the two groups. The sensor values were lower before breakfast in the bedtime group (180.5 ± 49.0 vs 223.8 ± 47.3 mg/dl, p=0.03). There were 13.7 events.patient ⁻¹.day⁻¹ in the bedtime group and 6.9 events.patient ⁻¹.day⁻¹ in the breakfast group in which glucose levels fell below 60 mg/dl (p=0.3). There were 121.6 events.patient ⁻¹.day⁻¹ in the bedtime group and 162.4 events.patient ⁻¹.day⁻¹ in the breakfast group in which glucose levels exceeded 180 mg/dl (p=0.05). Nighttime hypoglycemia only reached to a statistical significance between the two groups between 24:00 and 04:00. There were no significant correlations between the duration of nocturnal hypoglycemia, age, duration of diabetes, gender and HbA1c levels. Conclusion: Breakfast group is hyperglycemic during the day and hyperglycemia starts in the morning at 04:00. There is no significant difference in the frequency or duration of hypo/hyper glycemia during the day and night irrespective of the timing of glargine injection except pre−breakfast levels are significantly better in the bedtime group and hypoglycemia occurs between midnight and 04:00 in the bedtime group.Conflict of interest:None declared.     

A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients : A placebo-controlled, forced titration study

The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a long-lasting binding to the human AT₁-receptor, to that of losartan on ambulatory BP (ABP) not only during the 24-h dosing interval but also during the day of a missed dose intake. After a 4-week placebo lead-in period, 268 patients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP ≥85 mm Hg were randomized to receive either 8 mg of candesartan, 50 mg of losartan, or placebo for a 4-week period. Thereafter, the doses were doubled in all patients for an additional 4-week period. Ambulatory BP monitoring was performed for 36 h after dosing and clinic BP measured 48 h after dosing.

Candesartan cilexetil (16 mg) reduced ABP to a significantly greater extent than 100 mg of losartan, particularly for systolic ABP during daytime (P < .05), nighttime (P < .05), and 24-h (P < .01) periods, systolic (P < .01) and diastolic (P < .05) ABP between 0 and 36 h, and both systolic (P < .001) and diastolic (P < 0.001) ABP during the day of a missed dose. Clinic BP at 48 h after dosing was significantly reduced exclusively with 16 mg of candesartan. The differences in BP reduction between 8 mg of candesartan and 50 mg of losartan were statistically significant for systolic ABP during daytime (P < .01), nighttime (P < .05), 24-h (P < .01), 0 to 36 h (P < .05) and during the day of missed dose (P < .05). Moreover, although losartan did not significantly reduce ambulatory BP in a dose-related manner, ambulatory systolic and diastolic BP reductions with 16 mg of candesartan were significantly greater (P < .01 and < .001) than those seen with 8 mg of candesartan during every period at the ABP supporting a dose–response relationship.

In conclusion, this forced titration study in ambulatory hypertensive patients demonstrates that candesartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan cilexetil is superior to losartan in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose. The differences observed between both agents are most likely attributable to a tighter binding to, and a slower dissociation from, the receptor binding site with candesartan cilexetil.     

中西医结合治疗肺结核的临床疗效研究

目的:评价常规化疗方案联合中成药“抗痨合剂”及中医适宜技术治疗肺结核的临床疗效。方法:采用前瞻性研究的方法,连续纳入2017年1月至2019年12月浙江中医药大学附属丽水中医院结核科诊治的300例初治肺结核患者,采用随机数字表法将患者均等分成3组,即常规西药抗结核治疗组(A组)、常规西药抗结核治疗联合中成药抗痨合剂组(B组)、常规西药抗结核治疗联合中成药抗痨合剂及中医适宜技术组(C组)。剔除24例因诊断变更、中断治疗、发生药物不良反应患者后最终纳入276例患者,其中A组97例、B组93例、C组86例。观察并比较三组患者疗程末的中医症状改善情况、肺部病灶吸收情况、T淋巴细胞亚群变化及治疗转归情况。结果:治疗6个月后,B组和C组中医证状改善有效率[92.5%(86/93)和94.2%(81/86)]、肺部病灶吸收有效率[92.5%(86/93)和94.2%(81/86)]、CD3⁺T淋巴细胞百分比[(65.76±5.42)%和(67.06±5.95)%]、CD4⁺T淋巴细胞百分比[(44.97±5.35)%和(46.51±5.26)%]、治疗成功率[94.6%(88/93)和97.7%(84/86)]均明显优于A组[分别为82.5%(80/97)、76.3%(74/97)、(63.80±4.57)%、(42.72±4.82)%、80.4%(78/97)],差异均有统计学意义(χ²=2.000,P=0.046;χ²=2.999,P=0.003;χ²=2.427,P=0.015;χ²=2.886,P=0.004;t=2.699,P=0.008;t=4.186,P=0.005;t=3.048,P=0.003;t=6.428,P<0.001;χ²=2.069,P=0.039;χ²=2.192,P=0.028)。而B组和C组治疗后外周血CD8⁺T淋巴细胞百分比[(27.12±2.32)%和(26.35±3.17)%]均明显低于A组[(29.12±2.21)%],差异有统计学意义(t=5.051,P<0.001;t=9.231,P<0.001)。结论:中西药联合抗结核治疗可明显减轻肺结核患者的临床症状,促进肺部病灶吸收,提高肺结核患者免疫力,有效提高临床疗效,但中医适宜技术的应用效果未得到证实。     

Anaemia is an independent predictor of poor outcome in patients with chronic heart failure

Background: Mild anaemia frequently occurs in patients with chronic heart failure (CHF), particularly in the advanced stages of the disease. The correction of anaemia with erythropoietin is a therapeutic possibility. The aim of this study was to assess prospectively the relationship between the prevalence of anaemia (haemoglobin level≤120 g/l) and prognosis in an unselected CHF population. Methods: All consecutive patients with a diagnosis of CHF admitted to our department between January 2000 and April 2000 were considered for the present study. Those with secondary causes of anaemia were excluded. Patients were followed up until November 2001 (>18 months in all survivors), and the end-point of the study was all-cause mortality. Results: A total of 176 patients were enrolled (mean age: 63 years, New York Heart Association (NYHA) classification I/II/III/IV: 15/81/51/29; left ventricular ejection fraction (LVEF): 42%, ischaemic aetiology in 62%). In the whole population the mean haemoglobin level was 140±15 g/l. Anaemia was found in 18 (10%) patients, and was significantly more common in women than in men (18 vs. 7%, respectively, P=0.02) and in those with most severe CHF symptoms (frequency in NYHA I/II/III/IV: 0/9/10/21%, respectively; NYHA IV vs. I–III, P=0.03), but not related to the other clinical indices. Univariate analysis revealed NYHA class III–IV (hazard ratio 3.8, 95% CI: 1.6–8.9, P=0.003), low LVEF <35% (hazard ratio 2.3, 95% CI: 1.0–4.9, P=0.04) and anaemia (hazard ratio 2.9, 95% CI: 1.2–7.2, P=0.02) as predictors of 18-month mortality. In multivariate analysis, anaemia remained an independent predictor of death when adjusted for NYHA class and LVEF (hazard ratio: 2.6, 95% CI: 1.0–6.5, P=0.04). In anaemic patients, 18-month survival was 67% (95% CI: 45–89%) compared to 87% (81–92%) in patients with a normal haemoglobin level (P=0.016). Conclusions: Mild anaemia is a significant and independent predictor of poor outcome in unselected patients with CHF. Correction of low haemoglobin level may become an interesting therapeutic option for CHF patients.     

微卡免疫干预辅助治疗初治涂阴肺结核4个月治疗方案的疗效研究

目的: 评价微卡(注射用母牛分枝杆菌菌苗)免疫干预辅助治疗涂阴肺结核4个月治疗方案的临床疗效、药物不良反应及随访1年和2年复发情况,为缩短涂阴肺结核患者的疗程提供依据。 方法: 以2014年11月至2016年4月在湖南省邵东县和岳阳县结核病定点医疗机构诊断为初治涂阴肺结核的连续病例为研究对象,按纳入顺序在“德派(DAP)流行病学研究系统”进行登记录入,由系统随机分配到观察组(微卡免疫辅助方案组)和对照组(标准方案组),其中观察组184例,采用2H-R-Z-E/2H-R联用微卡治疗方案,对照组180例,采用2H-R-Z-E/4H-R治疗方案。比较两组患者治疗强化期末、疗程末的临床疗效和药物不良反应,以及疗程结束后随访1年和2年的复发情况。 结果: 共纳入患者364例,其中男性292例(80.2%),女性72例(19.8%),平均年龄(54±17)岁;在强化期末和疗程末,观察组的症状改善率分别为86.1%(130/151)和96.0%(145/151);对照组分别为86.5%(128/148)和95.3%(141/148),两组差异均无统计学意义(χ²值分别为0.010,0.103;P值分别为0.921,0.749)。观察组的胸部X线摄片病灶吸收率分别为19.0%(35/184)和41.3%(76/184),对照组分别为18.9%(34/180)和41.7%(75/180),两组差异无统计学意义(χ²值分别为0.100,0.005;P值分别为0.920,0.944)。观察组强化期末和疗程末的CD4⁺T淋巴细胞计数分别为(643.3±207.1)个/μl和(698.5±208.9)个/μl;对照组分别为(600.5±183.2)个/μl和(625.2±177.9)个/μl,两组差异均无统计学意义(t值分别为1.023,1.766;P值分别为0.309,0.081)。疗程末两组的成功治疗率均为100.0%(184/184,180/180)。疗程结束后观察组病例随访1年累计复发率0.6%(1/174),两年累计复发率1.2%(2/167);对照组随访1年累计复发率1.2%(2/172),两年累计复发率1.8%(3/164),差异均无统计学意义(Fisher精确概率法,P值分别为0.621和0.683)。疗程中观察组和对照组药物不良反应发生率分别为19.6%(36/184)和28.3%(51/180),差异有统计学意义(χ²=3.846,P<0.05)。 结论: 微卡免疫干预辅助治疗初治涂阴肺结核4个月治疗方案的临床疗效不劣于6个月标准治疗方案,且药物不良反应发生率低。     

Postprandial cholesteryl ester transfer and high density lipoprotein composition in normotriglyceridemic non-insulin-dependent diabetic patients

Altered postprandial HDL metabolism is a possible cause of defective reverse cholesterol transport and increased cardiovascular risk in diabetic patients with a normal fasting lipoprotein profile. Ten normolipidemic, normoponderal non-insulin dependent diabetes mellitus (NIDDM) patients and seven controls received a 980 kcal meal containing 78 g lipids with 100000 IU vitamin A. Chylomicron clearance was not different, but area under the curve (AUC) for retinyl palmitate in chylimicron-free serum (remnant clearance) was greater in patients (P < 0.02). LCAT activity increased postprandially to the same extent in both groups. In control subjects, cholesteryl ester transfer protein (CETP) activity (CETA) also increased by 20% (P < 0.01 at 6 h) in parallel with a 20% decrease in HDL₂-CE (r= −0.55, P = 0.009). In NIDDM patients, on the contrary, CETA which was 35% higher in the fasting state (P < 0.005), decreased postprandially yet HDL₂-CE remained unchanged. Postprandial HDL₃ of controls were enriched with phospholipid (PL) (30.3 ± 2.6% at 6 h) with respect to fasting (25.6 ± 2.5%, P < 0.01) and to NIDDM-HDL₃ (25.8 ± 1.7% at 6 h, P < 0.01). These results show that variation in plasma CETA has little impact on HDL₂-CE in NIDDH subjects. They support the concept that, in controls, the combined enrichment of HDL₃ with PL, increased LCAT and CETA create the conditions for stimulation of cell cholesterol efflux and CE transfer to apo B lipoproteins. In NIDDM, because of the lesser HDL₃ enrichment with PL and of the inverse trend of CETA, these conditions fail to occur, depriving the patients of a potentially efficient mechanism of unesterified cholesterol (UC) clearance, despite their strictly normal preprandial profile.