Compromised quality of life in patients with both Type 1 diabetes mellitus and coeliac disease.

AIMS: Type 1 diabetes mellitus and coeliac disease are two chronic illnesses associated with each other. Both diseases and their treatments can seriously impair quality of life. The objective of the present study was to investigate health-related quality of life in adult patients diagnosed with both Type 1 diabetes and coeliac disease and compare this with healthy control subjects and control subjects who have Type 1 diabetes only. METHODS: A generic measure of health-related quality of life (RAND-36) and a measure of diabetes-specific quality of life (DQOL) questionnaires were sent to patients diagnosed with both Type 1 diabetes and coeliac disease. The control group consisted of patients with Type 1 diabetes without coeliac disease matched for age, gender and socio-economic status. Generic quality of life scores were compared with data from healthy Dutch control subjects. RESULTS: Fifty-seven patients with Type 1 diabetes and coeliac disease were included and no associations between clinical characteristics and quality of life were observed. Women reported a lower quality of life in social functioning, vitality and mental health than men (all P < 0.05). A lower diabetes-specific quality of life was observed regarding diabetes-related worries and social worries in patients with Type 1 diabetes and coeliac disease compared with patients with Type 1 diabetes. Compared with healthy control subjects, quality of life in patients with Type 1 diabetes and coeliac disease was significantly lower, particularly social functioning (Cohen's d = 0.76) and general health perception (Cohen's d = 0.86). CONCLUSIONS: The additional diagnosis of coeliac disease and treatment by gluten-free diet in adult patients with Type 1 diabetes has a considerable, negative impact on quality of life and diabetes-specific quality of life. Women are particularly affected and social functioning and general health perception is compromised.

Safety of insulin glulisine when given by continuous subcutaneous infusion using an external pump in patients with type 1 diabetes.

This twelve-week, European, multicenter, controlled, open-label, randomized (1 : 1), parallel-group trial compared the safety of insulin glulisine with insulin as part used in continuous subcutaneous insulin infusion. Patients with type 1 diabetes (n=59) and continuous subcutaneous insulin infusion experience (mean values: HbA1c 6.9 % [insulin glulisine: 6.8 % VS. insulin as part: 7.1 %]; age 45.8 years; body mass index 26.0 kg/m2) were enrolled. HbA1c levels at endpoint (insulin glulisine: 7.0 % VS. insulin as part: 7.2 %), daily insulin doses, blood glucose profiles and adverse event rates were similar in both groups. The median (minimum-maximum) catheter occlusion rate was low for insulin glulisine and insulin as part (0 [0 - 0.7] VS. 0 [0 - 1.1] occlusions/month. Unexplained hyperglycemia occurred in six insulin glulisine-treated patients and twelve insulin as part-treated patients. Patients were expected to change their catheters every 2 days (15 changes/month); the catheter change rate was similar for insulin glulisine and insulin as part (14.1 VS. 14.8 changes/month). The frequency of infusion site reactions and hypoglycemia, and the time between catheter changes were similar for both insulin forms. Diabetic ketoacidosis was not reported. This study supports the safety of insulin glulisine in continuous subcutaneous insulin infusion administered via an external pump in type 1 diabetes.

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

AIMS: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. METHODS: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.

[Continuous subcutaneous insulin infusion is sometimes a good choice in case of poorly regulated diabetes mellitus type I]. / Continue subcutane insuline-infusie soms goede optie bij slecht gereguleerde diabetes mellitus type I.

Continuous subcutaneous insulin infusion (CSII) was initiated in 3 patients with diabetes mellitus type I who experienced difficulties with their glucose regulation: a woman aged 26 years and two men aged 56 and 41 years. 2 patients responded very well, while the third, the youngest man, did not benefit. Although interest in CSII has been growing in recent years, considerable uncertainty exists about which patients will benefit from it. In most studies, patients have attained a lower HbA,, and fewer blood glucose fluctuations. Recently, the advantages of CSII have been confirmed in 2 large studies in patients with diabetes mellitus type I. Motivated patients in poor glycaemic control seem to benefit most from CSII. Some questions remain, especially whether these advantages can be confirmed in studies comparing CSII with injection regimens using the new long-acting insulin analogues. Motivated patients in poor control and those with an unpredictable daily life, needing a flexible mode of therapy, should not be denied a trial of CSII.

Quality of life and metabolic control in patients with diabetes mellitus type 1 treated by continuous subcutaneous insulin infusion or multiple daily insulin injections.

OBJECTIVE: To assess the quality of life and metabolic control in patients with diabetes mellitus type 1 on continuous subcutaneous insulin infusion (CSII) in comparison with patients on multiple daily insulin injections (MDII). RESEARCH DESIGN AND METHODS: The study included 49 patients (13 males, 36 females), aged 41.4+/-11.3 years (mean+/-SD) on CSII for >1 year and 79 patients (43 males, 36 females), aged 43.1+/-14.8 years on MDII for >1 year, from three Dutch diabetic clinics. There were no statistically significant differences in duration of diabetes, social class, level of education, marital status, smoking or recent admissions to hospital. The questionnaires used were a Diabetes Quality of Life scale adapted from the DCCT, the Diabetes Satisfaction Questionnaire (DTSQ), and the WHO Well-Being Questionnaire. HbA1c was measured with an HPLC method (reference range 4.3 to 6.1 %). RESULTS: Using two-sided t-tests no statiscally significant differences were found between the patients on CSII and MDII with respect to quality of life (version A (<30 years) 4.32+/-0.22 vs 4.20+/-0.30; version B (> or =30 years) 4.18+/-0.25 vs 4.29+/-0.28), well-being (48.59+/-9.23 vs 50.99 +/-8.70), satisfaction with treatment (5.10+/-0.69 vs 5.15+/-0.71) and HbA1c (8.14+/-1.51 vs 8.47+/-1.40). Frequency of daily blood glucose monitoring was slightly higher in CSII than in MDII patients (4.52+/-1.19 vs 3.60+/-1.47; p<0.0001). CONCLUSION: The present data indicate that patients on CSII have similar QoL based on questionnaires when compared with patients on MDII. These data suggest that in patients with less optimal control on MDII, converting the treatment strategy to CSII is not associated with decreased quality of life.

Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment (HOT) study.

BACKGROUND AND AIMS: The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement, however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring. METHODS: The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure

Optimized basal-bolus therapy using a fixed mixture of 75% lispro and 25% NPL insulin in type 1 diabetes patients: no favorable effects on glycemic control, physiological responses to hypoglycemia, well-being, or treatment satisfaction.

OBJECTIVE: To investigate the effects of a multiple injection regimen with a mixture of 75% lispro and 25% intermediate-acting insulin (lispro high mixture [HM]) before meals on glycemic control, physiological responses to hypoglycemia, well-being, and treatment satisfaction. RESEARCH DESIGN AND METHODS: We studied 35 type 1 diabetes patients. After an 8- to 10-week lead-in period, patients were randomized to HM or human regular insulin therapy for 12-14 weeks. During the lead-in and treatment periods, HbA1c levels and hypoglycemic frequencies were measured, and patients completed the Well-Being Questionnaire and the Diabetes Treatment Satisfaction Questionnaire. In 19 patients, responses to hypoglycemia were tested during stepped euglycemic-hypoglycemic clamps. RESULTS: HM treatment improved postprandial glycemia but had no effect on HbA1c, frequency of hypoglycemia, well-being, or treatment satisfaction. During experimental hypoglycemia, HM therapy was associated with a slightly lower total adrenaline response and a higher autonomic symptom threshold (i.e., the autonomic symptom response occurred at a lower blood glucose level) than human regular insulin therapy. We speculate that this effect resulted from an accumulation of insulin during the night. CONCLUSIONS: Multiple injection therapy with HM rather than human regular insulin before meals does not offer advantages regarding glycemic control, frequency of hypoglycemia, well-being, or treatment satisfaction. In addition, this regimen causes an attenuation of the adrenaline and autonomic symptom responses to hypoglycemia.

Effect of BMI, insulin dose and number of injections on glycaemic control in insulin-using diabetic patients. Studygroup Diabetes Rijnmond (SDR).

BACKGROUND: Strict glucose control is essential to the prevention of diabetic complications. The level of glycaemic control in insulin-treated patients with diabetes mellitus (DM) in a routine clinical setting is not known. METHODS: In a cross-sectional survey comprising 8 hospitals in the Rijnmond area, The Netherlands, age, body mass index (BMI), insulin dose, number of injections, and HbA1c were scored in 712 patients with insulin-dependent DM (IDDM) and 462 patients with non-insulin-dependent DM (NIDDM). RESULTS: In IDDM and NIDDM patients, respectively, age (mean +/- SD) was 40 +/- 17 and 65 +/- 12 years, BMI was 24.1 +/- 3.5 and 27.3 +/- 4.1 kg/m2, daily insulin dose was 49 +/- 18 and 44 +/- 18 U (P < 0.001). Intensive therapy (> or = 4 injections or continuous subcutaneous insulin infusion) was used in 59% of IDDM and 13% of NIDDM patients. HbA1c below the upper normal limit was achieved in 11% of the patients, and within 20% above the upper normal limit in 37%. Obesity was positively associated with HbA1c in NIDDM patients (P < 0.01). A higher insulin dose was associated with higher HbA1c in both IDDM and NIDDM patients (P < 0.01). CONCLUSIONS: Good glycaemic control was established in 37% of our patients. Intensive insulin treatment and higher insulin dose did not improve glucose regulation. Obesity is a risk factor for poor glycaemic control.

The effect of GHRH on TSH release in rats in vivo and in vitro.

In man, GHRH has been shown to potentiate the TSH-releasing activity of TRH. To study the way by which GHRH affects TRH-stimulated TSH release, we examined the effect of GHRH (1-29)NH2 on basal and stimulated TSH secretion in intact male rats and superfused dispersed rat pituitary cells. In the intact rats, GHRH(1-29)NH2 potentiated TRH-stimulated TSH release in the evening, but potentiation was not observed in the morning and in dispersed pituitary cells. Basal TSH levels were not changed by GHRH(1-29)NH2. It is concluded that GHRH(1-29)NH2 potentiates the TSH-releasing activity of TRH in the evening in rats possibly through suprahypophyseal disinhibition.

Efficacy and safety of benazepril plus hydrochlorothiazide versus benazepril alone in hypertensive patients unresponsive to benazepril monotherapy.

A combination of benazepril 10 mg plus hydrochlorothiazide 12.5 mg once daily was investigated in the treatment of patients with mild-to-moderate essential hypertension who had not responded to monotherapy with benazepril 10 mg. Patients failing to respond to 4 weeks of benazepril 10 mg/d were randomized to continue with the monotherapy (n = 47) or receive the combination therapy (n = 46). After 4 weeks of double-blind treatment, reductions in blood pressure were significantly greater among patients given the combination than among those receiving benazepril alone: a 4.7 +/- 1.5 mm Hg difference in mean sitting diastolic blood pressure was noted in favor of the combination therapy (P = 0.0037). The incidence of adverse events, particularly cough, was lower with benazepril + hydrochlorothiazide than with benazepril alone; no notable changes in body weight or heart rate were seen in either group.

Octreotide scintigraphy for the detection of paragangliomas.

Paragangliomas have neuroendocrine characteristics. We previously described successful in vivo visualization of various tumors of neuroendocrine origin after injection of the radiolabeled somatostatin analogue octreotide. In this study, we report the results of 111In-octreotide scintigraphy in 34 patients referred because of known paragangliomas or in whom a paraganglioma was suspected and compared the results of octreotide scintigraphy with the outcomes of other imaging techniques used in the diagnosis or follow-up of these patients. Fifty of 53 (94%) known localizations in 25 patients with paragangliomas were visualized. In two patients, three localizations were missed during octreotide scintigraphy. Unexpected additional paraganglioma sites, not detected or not investigated with conventional imaging techniques, were found in 9 of 25 patients (36%) with known paragangliomas. In four of them, the supposed tumor localizations were thereafter also demonstrated with other imaging modalities. In eight of nine patients who were referred because of symptoms consistent with paraganglioma or follow-up after surgical removal of a paraganglioma, neither routine imaging nor octreotide scintigraphy revealed any abnormalities indicative of paraganglioma. We conclude that: (1) virtually all paragangliomas can be visualized using in vivo 111In-octreotide scintigraphy and (2) because conventional imaging is usually limited to the site where a paraganglioma is clinically suspected, octreotide scintigraphy, because of the information it provides on potential tumor sites in the whole body, may be useful in detecting multicentricity or metastases in patients with paraganglioma.

MRI screening of kindred at risk of developing paragangliomas: support for genomic imprinting in hereditary glomus tumours.

Paragangliomas of the head and neck (glomus tumours) can occur in a hereditary pattern and may be hormonally active as well as being associated with paragangliomas elsewhere. A number of these tumours may be present without symptoms. To detect the presence of subclinical paragangliomas we screened 83 members of a family at risk of developing hereditary paragangliomas using whole body MRI and urinary catecholamine testing. In eight previously diagnosed members, eight known glomus tumours of which one functioning, and two unknown glomus tumours and one unknown pheochromocytoma were present. Six unsuspected members showed ten glomus tumours and one pheochromocytoma. It has been suggested that the manifestation of hereditary glomus tumours is determined by the sex of the transmitting parent. There were no tumours in the descendants of female gene carriers. Comparing the likelihood of inheritance with genomic imprinting versus inheritance without genomic imprinting we found an odds ratio of 23375 in favour of genomic imprinting.

MR imaging and MIBG scintigraphy of pheochromocytomas and extraadrenal functioning paragangliomas.

To compare the potential of magnetic resonance (MR) imaging and scintigraphy performed with radiotracer-labeled metaiodobenzyl-guanidine (MIBG) in localization and characterization of functioning paragangliomas, the authors analyzed results of both modalities in 33 patients. Overall sensitivity for detection was 91% for MR imaging and 80% for MIBG scintigraphy. MR imaging demonstrated 100% of adrenal paragangliomas and 75% of extraadrenal paragangliomas, whereas MIBG scintigraphy revealed 75% and 88%, respectively. MIBG scintigraphy was more specific in the characterization of paragangliomas than MR imaging (100% vs 82%). However, MR imaging demonstrated nine other lesions not seen on scintigrams. On the basis of their results and other considerations, the authors believe MR imaging is the preferred initial technique when a functioning paraganglioma is suspected.

Iodine-123-metaiodobenzylguanidine scintigraphy in patients with chemodectomas of the head and neck region.

While studying the uptake of iodine-123-metaiodobenzylguanidine ([123I]MIBG) in chemodectomas, we coincidentally detected catecholamine secreting tumors in 5 out of 14 patients. In three of these cases, a norepinephrine secreting abdominal paraganglioma was subsequently removed. One patient had a norepinephrine secreting chemodectoma and one had a dopamine secreting chemodectoma. Prior to [123I]MIBG imaging and urinary catecholamine measurements, endocrine activity was suspected in only one of these five patients. Apart from these five cases, two other patients showed elevated catecholamine secretion and abnormal abdominal [123I]MIBG concentrations. However, these two patients were not surgically explored, because of normal computed tomography (CT) and magnetic resonance (MRI) studies. We suspect that catecholamine-secreting tumors are more common in patients with chemodectomas than is assumed in the literature, and we therefore recommend urinary catecholamine screening for all patients with chemodectomas. In case of elevated catecholamine secretion, MIBG scintigraphy is indicated.

Physiological effects of short-term treatment with enalapril in hypertensive patients.

To assess the effects of enalapril eight hospitalized hypertensive patients on constant sodium intake were treated with incremental doses of this angiotensin converting enzyme blocking drug. After four days of placebo treatment enalapril was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the 1.25 mg dose, angiotensin II (AII) and blood pressure did not change significantly, despite a 50% reduction in converting enzyme activity. There were, however, significant increases in noradrenaline, renin and aldosterone. With high doses a more pronounced reduction in converting enzyme activity was found while AII, aldosterone and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension did not occur. With continued treatment renal vascular resistance decreased concurrently with enhanced natriuresis and a reduction in body weight. Plasma volume rose slightly. The data indicate that enalapril may lower blood pressure by converting enzyme inhibition, but sodium loss and a decrease in sympathetic activity are associated features.

Humoral and renal effects of MK-421 (enalapril) in hypertensive subjects.

To assess the effect of MK-421 (enalapril) we treated six hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin-converting enzyme blocking drug. After a few days of placebo treatment, MK-421 was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the lowest dose, converting enzyme activity was reduced by 50%, but angiotensin II and blood pressure did not change significantly. There were, however, significant increases in noradrenaline, renin, and aldosterone. With higher doses there was a more pronounced reduction in converting enzyme activity, while angiotensin II, aldosterone, and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension was not observed. With continued treatment, renal vasodilatation and enhanced natriuresis occurred together with a 1.2 kg decrement in body weight. Concurrently plasma volume rose, but renal blood flow remained unchanged. The data indicate that MK-421 effectively lowers blood pressure, and it does so by converting enzyme inhibition; sodium loss and a decrease in sympathetic activity are associated features. Since plasma volume increased despite enhanced natriuresis, the drug may act both at the arteriolar and at the venular level.

Neurohumoral response to hospitalization in hypertensive patients.

1. To investigate whether reduced activity of pressor systems could explain the spontaneous drop in pressure upon hospitalization, 51 subjects with uncomplicated essential hypertension were admitted to hospital. Sodium intake was fixed at 55 mmol/day. 2. Blood samples for noradrenaline, adrenaline, active renin, angiotensin II and aldosterone were drawn on each morning of the first 3 days of hospitalization; blood pressure was measured at 2 h intervals and values were averaged for each day. 3. Subjects were divided in two groups depending on whether they became normotensive (group 1; n = 12) or remained hypertensive (group 2; n = 39). This distinction was thought to reflect mild and more severe hypertensive groups respectively. 4. Although both groups showed a comparable fall in blood pressure during hospitalization, noradrenaline levels fell more consistently in group 1, whereas adrenaline levels fell only in group 2. The components of the renin--angiotensin--aldosterone system rose, but more conspicuously in group 1. 5. It is concluded that withdrawal of sympathetic activity can only partly explain the hypotensive response to hospitalization. The renin--angiotensin system behaves only passively and appears to be counterproductive to alterations in blood pressure.