Parental sleep quality and continuous glucose monitoring system use in children with type 1 diabetes

To compare sleep quality and sleep–wake patterns in parents of children with type 1 diabetes before routine use of the continuous glucose monitoring system (CGMS) and while using it. Thirteen parents completed the Pittsburg Sleep Quality Index (PSQI), a 7-day sleep diary, and wore an actigraph (a wristwatch-size motion detector) during the night for 1 week before pediatric use of CGMS and 4–8 weeks after initiating routine use of the CGMS. Mean age of parents (ten mothers, three fathers) was 39 (range 32–47) years; mean age of children was 9.3 years (range 5.5–16.5 years); mean disease duration was 3.4 (range 0.6–11.2) years. PSQI total score demonstrated similar quality of sleep with and without use of the CGMS (4.6 and 4.9, respectively, p = 0.45). Six of the 13 parents reported severe sleep problems (PSQI ≥ 5) with and without the CGMS. The sleep diary indicated a greater number of awakening episodes during CGMS use than without the CGMS (1.6 and 1, respectively, p = 0.03), and actigraphy documented an increase in the number of wake bouts (22.9 and 19.7, p = 0.03) as well as in total wake time (48.3 and 42.2 min, p = 0.03) during CGMS use as compared with the period prior to CGMS use. Although self-perception of sleep quality remained unchanged, CGMS use appeared to affect actual parental sleep continuity somewhat negatively. This should be made clear to parents who may hold expectations of improvement in sleep quality following initiation of CGMS use.     

The effect of two new glucosidase inhibitors on blood glucose in healthy volunteers and in type II diabetics

Summary Two new glucosidase inhibitors (BAY m 1099 and BAY o 1248) were studied in volunteers and type II diabetics under various conditions. In 6 non-diabetic controls BAY m 1099 when given 3×50 mg/day caused a marked depression of the post-meal glucose rise. The effect was found to be more marked after breakfast than after lunch or after dinner. In type II diabetics BAY m 1099, when given in a dose of 2×25 mg/day over one week, had no significant effect on post-meal glucose or serum insulin levels. BAY o 1248, when given as a single dose of 15 mg in the morning to type II diabetics, induced a significant decrease of post-meal glucose rise (35 mg/dl after breakfast, 25 mg/dl after lunch) when compared to placebo. Although in parallel serum insulin levels were slightly lower, this change was statistically not significant. The drug reduced glycosuria by 50%. Both compounds induced side effects, such as flatulence or diarrhea when given in therapeutically effective amounts, but were tolerable in most cases. On a weight basis BAY o 1248 was found to have greater therapeutic effects than BAY m 1099. Both drugs can be recommended for use in unsatisfactorily controlled type II diabetics. Further studies should concentrate on the critical dosage which may strike a satisfactory balance between effects and side effects.     

Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis – a randomized, double-blind placebo-controlled study

Abstract:  Cystic fibrosis (CF) is a chronic progressive disorder characterized by repeated episodes of respiratory infection. Impaired sleep is common in CF leading to reduced quality of life. Melatonin, a secretory product of the pineal gland, has an important function in the synchronization of circadian rhythms, including the sleep–wake cycle, and has been shown to possess significant anti-oxidant properties. To evaluate the effects of exogenous melatonin on sleep and inflammation and oxidative stress markers in CF, a randomized double-blind, placebo-controlled study initially involving 20 patients with CF was conducted. One individual failed to conclude the study. All subjects were clinically stable when studied and without recent infectious exacerbation or hospitalization in the last 30 days. Groups were randomized for placebo ( n  = 10; mean age 12.1 ± 6.0) or 3 mg melatonin ( n  = 9; mean age 16.6 ± 8.26) for 21 days. Actigraphy was performed for 6 days before the start of medication and in the third week (days 14–20) of treatment. Isoprostane and nitrite levels were determined in exhaled breath condensate (EBC) at baseline (day 0) and after treatment (day 21). Melatonin improved sleep efficiency ( P  = 0.01) and tended to improve sleep latency ( P  = 0.08). Melatonin reduced EBC nitrite ( P  = 0.01) but not isoprostane. In summary, melatonin administration reduces nitrite levels in EBC and improves sleep measures in clinically stable CF patients. The failure of melatonin to reduce isoprostane levels may have been a result of the low dose of melatonin used as a treatment.     

Characterization of the antioxidant effects of melatonin and related indoleamines in vitro

Abstract: The antioxidant and possible pro-oxidant effects of melatonin and related indoleamines (tryptophan, serotonin, N-acetylserotonin, and 5-methoxytryptamine) were studied in vitro. In two model membrane systems, i.e., phospholipid liposomes and rat erythrocytes, lipid peroxidation induced by Fe²⁺ and H₂O₂, respectively, were reduced by the tested indoleamines except for tryptophan. The 5-hydroxy-indoleamines, serotonin, and N-acetylserotonin exhibited pro-oxidant actions in the bleomycin assay by reducing Fe³⁺ to Fe²⁺, which leads to DNA damage. The 5-methoxy-indoleamines, melatonin and 5-methoxytryptamine, were devoid of any pro-oxidant actions in this assay. Serotonin, but not N-acetylserotonin, scavenged the superoxide anion. None of the indoleamines tested had any reactivity towards H₂O₂. All the indoleamines, including tryptophan, were, however, shown to react with hypochlorous acid. These findings support an antiperoxidative and antioxidant action of melatonin which is devoid of pro-oxidant effect on non-lipid substrates.     

Nocturnal plasma melatonin concentrations in healthy volunteers: Effect of single doses of d-fenfluramine, paroxetine, and ipsapirone

Abstract: The effect on nocturnal melatonin secretion of acute administration of the indirectly acting serotonin (5-HT) receptor agonists d-fenfluramine (30 mg) and paroxetine (20 mg) and a partial 5-HT_1A receptor agonist ipsapirone (20 mg) was investigated in healthy male volunteers and compared to a placebo condition. Each subject (n=8) received each drug on one occasion over a 4 week study period, with drug administration separated by 1 week. A randomized, counter-balanced design was used. Drugs or placebo were administered at 2,000 hours in the light, and all blood samples were collected throughout the night in the dark at regular intervals until 0600 hours. Neither d-fenfluramine, paroxetine, or ipsapirone following acute dosage had a statistically significant effect on nocturnal melatonin synthesis. The lack of effect seen with d-fenfluramine, paroxetine, and ipsapirone may be due to limitations imposed by the dose requirements.     

Normalization of the sleep-wake pattern and melatonin and 6-sulphatoxy-melatonin levels after a therapeutic trial with melatonin in children with severe epilepsy

Abstract: This study evaluated the sleep–wake pattern, plasma melatonin levels and the urinary excretion of its metabolite, 6‐sulphatoxy‐melatonin among children with severe epileptic disorders, before and after a therapeutic trial with melatonin. Ten paediatric patients, suffering from severe epileptic disorders, were selected and given a nightly dose of 3 mg of a placebo, for 1 wk; for the next 3 months, the placebo was replaced with a nightly dose of 3 mg of melatonin. At the end of each treatment period, the urinary excretion of 6‐sulphatoxy‐melatonin (for the intervals 09.00 – 21:00 hr or 21:00–09:00 hr) and plasma levels of melatonin (recorded at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00 hr) were recorded, over a period of 24 hr; an actigraph record was also kept. Sleep efficiency among patients who received melatonin was significantly higher than among those given the placebo, with fewer night‐time awakenings. Periodic plasma melatonin levels were regained and a better control gained of convulsive episodes, in that the number of seizures decreased. We conclude that melatonin is a good regulator of the sleep–wake cycle for paediatric patients suffering from severe epilepsy, moreover, it to a better control of convulsive episodes.     

Preclinical Efficacy of Melatonin to Reduce Methotrexate-Induced Oxidative Stress and Small Intestinal Damage in Rats

Background

Methotrexate is widely used as a chemotherapeutic agent for leukemia and other malignancies. The efficacy of this drug is often limited by mucositis and intestinal injury, which are the major causes of morbidity in children and adults.

Aim

The present study investigates whether melatonin, a powerful antioxidant, could have a protective effect.

Method

Rats were pretreated with melatonin (20 and 40 mg/kg body weight) daily 1 h before methotrexate (7 mg/kg body weight) administration for three consecutive days. After the final dose of methotrexate, the rats were sacrificed and the small intestine was used for light microscopy and biochemical assays. Intestinal homogenates were used for assay of oxidative stress parameters malondialdehyde and protein carbonyl content, and myeloperoxidase activity, a marker of neutrophil infiltration as well as for the activities of the antioxidant enzymes.

Result

Pretreatment with melatonin had a dose-dependent protective effect on methotrexate (MTX)-induced alterations in small intestinal morphology. Morphology was saved to some extent with 20 mg melatonin pretreatment and near normal morphology was achieved with 40 mg melatonin pretreatment. Biochemically, pretreatment with melatonin significantly attenuated MTX-induced oxidative stress (P < 0.01 for MDA, P < 0.001 for protein carbonyl content) and restored the activities of the antioxidant enzymes (glutathione reductase P < 0.05, superoxide dismutase P < 0.01).

Conclusion

The results of the present study demonstrate that supplementation by exogenous melatonin significantly reduces MTX-induced small intestinal damage, indicating that it may be beneficial in ameliorating MTX-induced enteritis in humans.     

Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts

Melatonin is an animal hormone as well as a signaling molecule in plants. It was first identified in plants in 1995, and almost all enzymes responsible for melatonin biosynthesis had already been characterized in these species. Melatonin biosynthesis from tryptophan requires four‐step reactions. However, six genes, that is, TDC, TPH, T5H, SNAT, ASMT, and COMT, have been implicated in the synthesis of melatonin in plants, suggesting the presence of multiple pathways. Two major pathways have been proposed based on the enzyme kinetics: One is the tryptophan/tryptamine/serotonin/N‐acetylserotonin/melatonin pathway, which may occur under normal growth conditions; the other is the tryptophan/tryptamine/serotonin/5‐methoxytryptamine/melatonin pathway, which may occur when plants produce large amounts of serotonin, for example, upon senescence. The melatonin biosynthetic capacity associated with conversion of tryptophan to serotonin is much higher than that associated with conversion of serotonin to melatonin, which yields a low level of melatonin synthesis in plants. Many melatonin intermediates are produced in various subcellular compartments, such as the cytoplasm, endoplasmic reticulum, and chloroplasts, which either facilitates or impedes the subsequent enzymatic steps. Depending on the pathways, the final subcellular sites of melatonin synthesis vary at either the cytoplasm or chloroplasts, which may differentially affect the mode of action of melatonin in plants.     

Effect of soy-based breakfast cereal on blood lipids and oxidized low-density lipoprotein

Consumption of soy protein may reduce the risk of cardiovascular disease both through reduction in serum lipids and by the antioxidant properties of protein-associated soy isoflavones. However, the effect that processing required for the manufacture of breakfast cereals may have on the lipid lowering and antioxidant activities of soy has not been studied. We have therefore assessed the health benefits of soy incorporation into breakfast cereals. Twenty-five hyperlipidemic men and women took soy (providing 36 g/d soy protein and 168 mg/d isoflavones) and control breakfast cereals, each for 3 weeks in a randomized crossover study with a 2-week washout period between treatments. Fasting blood samples were obtained pretreatment and at weeks 2 and 3 of each treatment. No significant difference was seen in serum lipids between treatments at week 3 apart from a 3.8% +/- 1.5% higher apolipoprotein A-1 level on control versus soy (P = .021). However, oxidized low-density lipoprotein (LDL) was reduced on the test compared with the control both as total dienes in LDL and as the ratio of conjugated dienes to cholesterol in the LDL fraction by 9.2% +/- 4.3% (P = .042) and 8.7% +/- 4.2% (P = .050), respectively. High isoflavone intakes in soy breakfast cereals may decrease the risk of cardiovascular disease by reducing oxidized LDL, while having no significant effect on the absolute concentration of LDL cholesterol.     

Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study

BACKGROUND AND AIMS: Melatonin, a sleep promoting agent, is involved in the regulation of gastrointestinal motility and sensation. We aimed to determine if melatonin was effective in improving bowel symptoms and sleep disturbances in irritable bowel syndrome (IBS) patients with sleep disturbance. METHODS: Forty IBS patients (aged 20-64 years; 24 female) with sleep disturbances were randomly assigned to receive either melatonin 3 mg (n = 20) or matching placebo (n = 20) at bedtime for two weeks. Immediately before and after the treatment, subjects completed bowel, sleep, and psychological questionnaires, and underwent rectal manometry and overnight polysomnography. RESULTS: Compared with placebo, melatonin taken for two weeks significantly decreased mean abdominal pain score (2.35 v 0.70; p<0.001) and increased mean rectal pain threshold (8.9 v -1.2 mm Hg; p<0.01). Bloating, stool type, stool frequency, and anxiety and depression scores did not significantly differ after treatment in both groups. Data from sleep questionnaires and polysomnography showed that the two week course of melatonin did not influence sleep parameters, including total sleep time, sleep latency, sleep efficiency, sleep onset latency, arousals, duration of stages 1-4, rapid eye movement (REM) sleep, and REM onset latency. CONCLUSIONS: Administration of melatonin 3 mg at bedtime for two weeks significantly attenuated abdominal pain and reduced rectal pain sensitivity without improvements in sleep disturbance or psychological distress. The findings suggest that the beneficial effects of melatonin on abdominal pain in IBS patients with sleep disturbances are independent of its action on sleep disturbances or psychological profiles.     

Effects of 4 weeks’ administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations

Summary The effects of 4 weeks' administration of pramlintide, an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 μg four times per day (breakfast, lunch, dinner, and evening snack), 30 μg three times per day (breakfast, lunch and dinner [BLD]), 30 μg three times per day (breakfast, dinner and evening snack [BDS]), and 60 μg twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 μg four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (– 1.4 ± 0.5 vs 0.3 ± 0.5 μmol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 ± 10 μmol/l in the pramlintide 30 mg four times per day group, 43 ± 7 μmol/l in the pramlintide 30 μg three times per day (BLD) group, 47 ± 6 μmol/l in the pramlintide 30 μg three times per day (BDS) group, 46 ± 7 μmol/l in the pramlintide 60 μg twice per day group, and 29 ± 8 μmol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA_1c as the measurement of glycaemic control are warranted. [Diabetologia (1997) 40: 1278–1285] Received: 3 January 1997 and in revised form: 2 May 1997     

Melatonin treatment for age-related insomnia

Older people typically exhibit poor sleep efficiency and reduced nocturnal plasma melatonin levels. The daytime administration of oral melatonin to younger people, in doses that raise their plasma melatonin levels to the nocturnal range, can accelerate sleep onset. We examined the ability of similar, physiological doses to restore nighttime melatonin levels and sleep efficiency in insomniac subjects over 50 yr old. In a double-blind, placebo-controlled study, subjects who slept normally (n = 15) or exhibited actigraphically confirmed decreases in sleep efficiency (n = 15) received, in randomized order, a placebo and three melatonin doses (0.1, 0.3, and 3.0 mg) orally 30 min before bedtime for a week. Treatments were separated by 1-wk washout periods. Sleep data were obtained by polysomnography on the last three nights of each treatment period. The physiologic melatonin dose (0.3 mg) restored sleep efficiency (P < 0.0001), acting principally in the midthird of the night; it also elevated plasma melatonin levels (P < 0.0008) to normal. The pharmacologic dose (3.0 mg), like the lowest dose (0.1 mg), also improved sleep; however, it induced hypothermia and caused plasma melatonin to remain elevated into the daylight hours. Although control subjects, like insomniacs, had low melatonin levels, their sleep was unaffected by any melatonin dose.     

Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis

Sepsis is a massive inflammatory response mediated by infection, characterized by oxidative stress, release of cytokines, and mitochondrial dysfunction. Melatonin accumulates in mitochondria, and both it and its metabolites have potent antioxidant and anti‐inflammatory activities and may be useful in sepsis. We undertook a phase I dose escalation study in healthy volunteers to assess the tolerability and pharmacokinetics of 20, 30, 50, and 100 mg oral doses of melatonin. In addition, we developed an ex vivo whole blood model under conditions mimicking sepsis to determine the bioactivity of melatonin and the major metabolite 6‐hydroxymelatonin at relevant concentrations. For the phase I trial, oral melatonin was given to five subjects in each dose cohort (n = 20). Blood and urine were collected for measurement of melatonin and 6‐hydroxymelatonin, and symptoms and physiological measures were assessed. Validated sleep scales were completed. No adverse effects after oral melatonin, other than mild transient drowsiness with no effects on sleeping patterns, were seen, and no symptoms were reported. Melatonin was rapidly cleared at all doses with a median [range] elimination half‐life of 51.7 [29.5–63.2] min across all doses. There was considerable variability in maximum melatonin levels within each dose cohort, but 6‐hydoxymelatonin sulfate levels were less variable and remained stable for several hours. For the ex vivo study, blood from 20 volunteers was treated with lipopolysaccharide and peptidoglycan plus a range of concentrations of melatonin/6‐hydroxymelatonin. Both melatonin and 6‐hydroxymelatonin had beneficial effects on sepsis‐induced mitochondrial dysfunction, oxidative stress, and cytokine responses at concentrations similar to those achieved in vivo.     

Tryptophan administration inhibits nocturnal N-acetyltransferase activity and melatonin content in the rat pineal gland. Evidence that serotonin modulates melatonin production via a receptor-mediated mechanism.

In the rat pineal gland, the activity of serotonin N-acetyltransferase (NAT) and the concentration of melatonin are normally high at night; conversely, the concentration of serotonin (5-HT), the precursor of melatonin, is low. Since tryptophan administration increases the concentration of pineal 5-HT at night, we examined its effect of melatonin production. Nighttime tryptophan loading led to substantial increases in pineal 5-hydroxytryptophan, 5-hydroxyindole acetic acid (5-HIAA), and 5-HT but a highly significant reduction in NAT activity in comparison to saline-injected controls. In contrast to other measured indoles, melatonin levels also were significantly diminished by tryptophan loading. Nocturnally high pineal norepinephrine levels were unaltered by tryptophan administration. The idea that high concentrations of 5-HT could lead to substrate inhibition of NAT activity was not supported by kinetic analysis of control NAT levels versus tryptophan-inhibited NAT activity under varied substrate concentrations. Hypotheses to explain these results include the possibility that tryptophan inhibition of melatonin synthesis is mediated by the release of 5-HT from the pinealocyte and its subsequent autocrine action on melatonin production.     

Clinical trials of controlled-release melatonin in children with sleep-wake cycle disorders

This is the first study to examine effective doses of controlled-release (CR) melatonin in children with chronic sleep wake cycle disorders. All 42 subjects had severe neurodevelopmental difficulties. Initially, a randomized double-blinded cross-over design was used in 16 children, comparing the effectiveness of fast-release (FR) and CR melatonin. In the remainder of the patients, the CR melatonin was studied on a clinical basis. The effectiveness of treatment was assessed by sleep charts and clinical follow-up. Emphasis was placed on the judgement of the parents, who had guidance from the physicians. The average final CR melatonin dose in the 42 patients was 5.7 mg (2-12 mg). The studies showed that the FR melatonin was most effective when there was only delayed sleep onset, but CR formulations were more useful for sleep maintenance. Children appeared to require higher doses than adults.     

STIMULATION OF C14-MELATONIN SYNTHESIS FROM C14-TRYPTOPHAN BY NORADRENALINE IN RAT PINEAL IN ORGAN CULTURE

Previous work has shown that the activity of the melatonin-forming enzyme in the rat pineal gland is elevated in rats kept in continuous darkness as compared to those kept in continuous light. Information about environmental lighting reaches the pineal gland via nerves that liberate noradrenaline. Rat pineal glands in organ culture can form C(14)-melatonin from C(14)-tryptophan as follows: tryptophan --> 5-hydroxytryptophan --> serotonin --> melatonin.Noradrenaline was found to stimulate the synthesis of C(14)-melatonin from C(14)-tryptophan in rat pineals in organ culture. Other compounds related in structure to noradrenaline increase melatonin and serotonin synthesis and inhibit the formation of the deaminated product of serotonin, 5-hydroxyindole acetic acid. Cycloheximide, a compound that inhibits protein synthesis, also prevents the formation of serotonin, melatonin, and 5-hydroxyindole acetic acid from tryptophan in pineal organ culture. These observations suggest that noradrenaline liberated from sympathetic nerves stimulates the formation of melatonin either by increasing the formation of new melatonin-forming enzyme, by increasing transport of tryptophan into the pineal cell, or by inhibiting the metabolism of serotonin by the alternate deaminating pathway.     

The role of tryptophan metabolism in postpartum depression

The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%–20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD. Importantly, an increase in stress hormones and immune-inflammatory activity drives tryptophan to the production of neuroregulatory kynurenine pathway products and away from the serotonin and melatonin pathways. This links the PPD to other disorders of depressed mood, which are classically associated with decreased serotonin and melatonin, coupled to increases in kynurenine pathway products. Several kynurenine pathway products, such as kynurenic acid and quinolinic acid, can have neuroregulatory effects, with consequences pathological underpinnings of the PPD. The current article reviews the role of alterations in tryptophan metabolism in the PPD.     

Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment

The objective of the present study was to assess the toxicology of melatonin (10 mg), administered for 28 days to 40 volunteers randomly assigned to groups receiving either melatonin (N = 30) or placebo (N = 10) in a double-blind fashion. The following measurements were performed: polysomnography (PSG), laboratory examinations, including complete blood count, urinalysis, sodium, potassium and calcium levels, total protein levels, albumin, blood glucose, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), urea, creatinine, uric acid, glutamic-oxalacetic transaminase (GOT), glutamic-pyruvate transaminase (GPT), bilirubin, alkaline phosphatase, gama-glutamic transaminase (GGT), T3, T4, TSH, LH/FSH, cortisol, and melatonin serum concentrations. In addition, the Epworth Somnolence Scale (ESS) and a sleep diary (SD) were also applied to the volunteers 1 wk before each PSG. In addition, the volunteers were asked about possible side effects (SE) that appeared during the treatment. The study was carried out according to the following timetable: Visit 0, filling out the term of consent and inclusion criteria; Visit 1, PSG, laboratory examinations, ESS, SD, melatonin serum concentrations; Visit 2, SD, melatonin serum concentrations, SE; Visit 3, melatonin serum concentrations, PSG, ESS, SE; Visit 4, laboratory examinations, SE, melatonin serum concentrations, SD; and Visit 5, PSG, ESS, SE. Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group. No other differences between the placebo and melatonin groups were obtained. In the present study we did not observe, according to the parameters analyzed, any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study.     

Diurnal variation of carbohydrate insulin ratio in adult type 1 diabetic patients treated with continuous subcutaneous insulin infusion

To estimate the carbohydrate‐to‐insulin ratio (CIR), a formula dividing a constant, usually 300–500, by the total daily dose (TDD) of insulin, is widely utilized. An appropriate CIR varies for each meal of the day, however. Here, we investigate diurnal variation of CIR in hospitalized Japanese type 1 diabetic patients treated with continuous subcutaneous insulin infusion. After optimization of the insulin dose, TDD and total basal insulin dose (TBD) were 34.9 ± 10.2 and 9.3 ± 2.8 units, respectively, with a percentage of TBD to TDD of 27.3 ± 6.0%. The products of CIR and TDD at breakfast, lunch and dinner were 311 ± 63, 530 ± 161, and 396 ± 63, respectively, suggesting that in the formula estimating CIR using TDD, the constant should vary for each meal of the day, and that 300, 500, and 400 are appropriate for breakfast, lunch, and dinner, respectively.