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Guar Gum in Non-Insulin-Dependent Diabetes Mellitus: A Double-Blind Crossover, Placebo-Controlled Trial in Saudi Arabian Patients

1990; King Faisal Specialist Hospital and Research Centre; Volume: 10; Issue: 5 Linguagem: Inglês

10.5144/0256-4947.1990.525

0975-4466

Mohamed A. Laajam, Lucia K. Jim, Souha El-Bolbol, Sami A. Bashi, Layla A. Al-Khayal, Omer Al-Attas, Riad A. Sulimani,

Diet and metabolism studies

Original ArticlesGuar Gum in Non-Insulin-Dependent Diabetes Mellitus: A Double-Blind Crossover, Placebo-Controlled Trial in Saudi Arabian Patients Mohamed A. Laajam, MRCP Lucia K. Jim, Pharm. D Souha El-Bolbol, B. Pharm Sami A. Bashi, MRCP Layla A. Al-Khayal, MBBS Omer S. Al-Attas, and PhD Riad A. SulimaniFRCP(C) Mohamed A. Laajam Address reprint requests and correspondence to: Dr. M. Laajam: Department of Medicine (38), College of Medicine, P.O. Box 2925, Riyadh 11461, Saudi Arabia. From the Department of Medicine, College of Medicine, King Saud University, Riyadh Search for more papers by this author , Lucia K. Jim From the Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh Search for more papers by this author , Souha El-Bolbol From the Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh Search for more papers by this author , Sami A. Bashi From the Department of Medicine, College of Medicine, King Saud University, Riyadh Search for more papers by this author , Layla A. Al-Khayal From the Department of Medicine, College of Medicine, King Saud University, Riyadh Search for more papers by this author , Omer S. Al-Attas From the Department of Biochemistry, College of Science, King Saud University, Riyadh Search for more papers by this author , and Riad A. Sulimani From the Department of Medicine, College of Medicine, King Saud University, Riyadh Search for more papers by this author Published Online:1 Sep 1990https://doi.org/10.5144/0256-4947.1990.525SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutAbstractWe conducted a double-blind crossover, placebo-controlled trial to evaluate the effects of guar gum, as a food additive, on glycemic control, plasma lipid concentration, and body weight in 39 Saudi patients with non-insulin-dependent diabetes mellitus. All subjects were overweight and their diabetes was uncontrolled on diet and maximum doses of oral hypoglycemic agents. Mean fasting plasma glucose (FPG) and glycosylated hemoglobin (HbAl) concentrations after treatment with guar were significantly lower than those seen with placebo (FPG: 11.00 ± 0.42 versus 12.70 ± 0.53 mmol/L; P < 0.01; HbAl: 11.00 ± 0.35% versus 11.90 ± 0.30%, P < 0.05). The postprandial plasma glucose level was also significantly lower when guar was added to an identical test meal than that observed with placebo (P < 0.02). The total plasma cholesterol level decreased from 5.76 ± 0.21 mmol/L prior to treatment to 5.00 ± 0.16 mmol/L (P < 0.01) at the end of treatment. There was no significant change in body weight during either phase of the study. Guar treatment was associated with a higher rate of side-effects in our study than have been previously reported, but this rate declined with time and the drug was well tolerated. We found guar to be a safe, useful, and effective adjunct in the management of patients with non-insulin-dependent diabetes mellitus that is uncontrolled with conventional therapy.IntroductionDiabetes mellitus is a major health problem in the Kingdom of Saudi Arabia1,2 and has a high rate of complications and morbidity, especially in patients whose disease is poorly controlled.3,6 Non-insulin-dependent diabetes (NIDD, type 2) is the predominant type in the Kingdom. When patients do not comply with their diet, are overweight, and do not exercise, maximum oral hypoglycemic therapy is usually ineffective in achieving satisfactory glycemic control. Carefully conducted studies have shown that fiber-supplemented diets improve glycemic control and decrease serum cholesterol levels in diabetics.7,8 Viscous fiber added to the diet has been found to slow postprandial glucose absorption.9 Of this group of nonabsorbable carbohydrates, guar has been shown to be the most effective in diminishing postprandial glycemic response, both in diabetic and nondiabetic, subjects.10,11 In addition, guar granules were shown to be more effective in lowering postprandial plasma glucose levels when simply sprinkled on the food, rather than taken as a “premeal drink.”10The effectiveness of guar in glycemic control, plasma lipid levels, and body weight was evaluated in overweight type 2 Saudi diabetics whose disease was not controlled by diet and maximally tolerated oral hypoglycemic agents.PATIENTS AND METHODSSixty-three Saudi patients with NIDD who were on oral hypoglycemic agents were recruited from the diabetes clinic at King Abdul Aziz University Hospital in Riyadh and selected according to the following criteria: (1) age, 21-70 years; (2) overweight-body mass index, > 24 kg/m; (3) treated with maximum tolerated doses of oral hypoglycemic agents for at least 6 months; (4) control of diabetes is considered moderate to poor (i.e., either FPG > 9 mmol/L or HbAl > 10%); (5) no clinical esophageal or other gut motility dysfunction; and (6) no condition that contraindicates the use of guar.Patients were excluded if they were pregnant or had recently undergone another drug therapy that might influence diabetic control.Only those patients who completed both phases of the study were included in the final analysis. Thirty-nine patients completed the study. Their mean fasting plasma glucose levels during three consecutive outpatient visits before the start of the study was 12.5 ± 3.0 mmol/L. All patients were on high doses of sulfonylureas, a majority of them in combination with metformin. No change in drug therapy or diet was made in any of the patients during the study period, unless hypoglycemia occurred. Informed consent was obtained from each subject before the start of the study. Characteristics of patients completing the study are summarized in Table 1.Table 1. Clinical data on 39 non-insulin-dependent diabetic patients.Table 1. Clinical data on 39 non-insulin-dependent diabetic patients.Study ProtocolConsecutive patients who met the inclusion criteria were allocated randomly to either a guar (Guarina; Norgine Ltd., Oxford, U.K.) treatment group or a placebo (beef gelatin) group. After 4 weeks, patients underwent a washout period of 4 weeks, then were crossed over to the opposite group and continued for 4 more weeks in a double-blind fashion. Patients were interviewed and weighed. Urine glucose, fasting plasma glucose, cholesterol, triglyceride, C-peptide, insulin, and glycosylated hemoglobin (HbAl) levels were measured, and routine biochemical and hematological determinations were done at the beginning and end of each phase of the study. Demographic data were also obtained.Patients were asked to bring all current medications to the clinic and were issued a new two-week supply of oral hypoglycemic agents. An adequate number of packets of guar or placebo and oral hypoglycemic agents, as well as oral and written instructions for their proper use, were given to patients. One 5-gm packet of guar or placebo was to be taken with each main meal three times daily, and the guar or placebo granules sprinkled evenly over food or stirred into semisolid foods (e.g., yoghurt). Patients were told to return to the clinic every two weeks after a 10-hour fast. At each visit, body weight and urine glucose and FPG levels were determined. A medication count was also done to assess compliance. The clinical pharmacist also assessed the incidence of side-effects. An appointment for the next clinic visit plus additional medications were provided. Patients were monitored in this way throughout the entire 12 weeks of the study.To evaluate the effect of guar gum on postprandial plasma glucose concentration, a standardized breakfast (approximately 400 calories) was provided during the second clinic visit at each study phase. Either a packet of guar or placebo was sprinkled onto the food before consumption and then the one-hour postprandial plasma glucose level was measured. The time taken to eat the breakfast was usually less than 20 minutes.In the event that patients dropped out of the study, the reasons for this were documented.Laboratory AssaysPlasma glucose, cholesterol, triglyceride levels, and renal and hepatic functions were estimated using a multichannel autoanalyzer (SMAC, Tech-nicon, USA). HbAl concentration was determined by an electrophoretic method (GLYT-RAC, Corning Medical, Palo Alto, CA, USA). Plasma C-peptide and total immunoreactive insulin were assayed using commercially available radioimmunoassay kits (DRG International, NJ, USA, and Amersham, Buckinghamshire, U.K., respectively). Hematological tests were carried out using a Coulter counter.Statistical AnalysisSince normally distributed variables were measured, Student’s t test for paired results was used. P < 0.05 was considered statistically significant.RESULTSCompliance, Side-effects, and Body WeightThirty-nine (28 females, 11 males) of 63 patients who had originally been recruited completed the study. The baseline parameters of the drop-out group were not significantly different from those in the patients who completed the study. Of the 24 patients who dropped out, 12 did so during the guar phase and 12 during the placebo phase. The main reasons for the dropout were inability to tolerate the drug in seven patients on guar and three on placebo. Eight patients failed to return, four did not comply with the drug regimen, one was admitted to the hospital for reasons unrelated to the diabetes, and one became pregnant.The main side effects are listed in Table 2. Most symptoms abated after a few days of continued treatment, and in only ten patients (seven on guar and three on placebo) was the treatment discontinued because of intolerance. There was no significant change in body weight for the study entrants during either phase of the study.Table 2. Number of patients with significant adverse effects during guar and placebo treatment.Table 2. Number of patients with significant adverse effects during guar and placebo treatment.Laboratory FindingsFPG and HbAl values are shown in Table 3. The values of both at the start of each treatment period were not significantly different. The FPG level decreased significantly from 12.50 ± 0.50 mmol/L to 11.00 ± 0.42 mmol/L at the end of the guar period, while levels before and after the placebo period remained the same. The HbAl level declined from 12.10 ± 0.42% to 11.00 ± 0.35% during the guar period, but no significant changes were observed during the placebo period. Figure 1 (A and B) shows the individual FPG and HbAl data at the beginning and end of both treatment periods. After guar treatment, all 39 patients showed a decrease in the values of FPG and HbAl, except 11 and 10, respectively.Table 3. Clinical data on patients at the beginning and end of each treatment period.Table 3. Clinical data on patients at the beginning and end of each treatment period.Figure 1. Individual changes in fasting plasma glucose (a). glycosylated hemoglobin (b), and cholesterol (c) in all 39 patients.Download FigureThe concentrations of total cholesterol and triglycerides were not significantly different at the start of either study period, but there was a significant decrease in the total cholesterol level of from 5.76 ± 0.21 mmol/L to 5.00 ± 0.16 mmol/L during guar treatment but not during placebo treatment (Table 3, Figure 1C). The cholesterol concentration at the end of the guar period was significantly lower than that observed at the end of the placebo period (P < 0.01). There was no significant change in the mean plasma triglyceride concentration during either study period.The one-hour postprandial plasma glucose level following guar ingestion was significantly lower than that observed following placebo treatment (14 ± 3.5 mmol/L versus 16.1 ± 3.5 mmol/L; P < 0.02). There was no change in the fasting plasma C-peptide and total immunoreactive insulin levels throughout the study (Table 3).No change in any biochemical or hematological variables was observed during either phase of the study in any patient.DISCUSSIONDiabetes mellitus represents a major disease in Saudi Arabia and predominantly occurs in the form of NIDD.1,3 From our experience, excessive weight, diet noncompliance, and lack of exercise are the major sources of difficulty in controlling the disease in most patients, especially among females. Any adjuvant treatment is welcome in those who are inadequately managed on maximally tolerated oral hypoglycemic agents. The possible role of guar in the management of diabetes was first suggested by Jenkins et al12 in 1976. Several later studies showed that guar gum improves both glycemic and blood lipid levels in diabetes.10,11,13–16 Guar is a non-cellulose, soluble dietary fiber that is extracted from the cluster bean. The most effective mode of guar administration is to mix it with food.9,13,17,18 Other modes of administration are associated with a high rate of side-effects,17 and do not seem to be as effective.19 For these reasons, we evaluated the use of guar in the form of granules mixed with main meals and its effectiveness in the metabolic control of patients with NIDD.Because of the anticipated lack of compliance in keeping clinic appointments, we started with a large number of patients. Of the total 63 patients recruited, 24 dropped out (38.1%). Since equal numbers of patients dropped out during the placebo and guar phases, the high attrition rate should not affect the statistical analysis of the study results. Half of the dropouts were due to noncompliance in attending the clinics or in taking the medications as instructed.Guar is a natural vegetable fiber that is classified chemically as a galactomannan. It has been shown to delay absorption of carbohydrates and reduce postprandial hyperglycemia and serum insulin levels.9,10 Jenkins et al9 demonstrated a positive correlation between the viscosity of various fibers and the mean percentage reduction of the maximum rise in blood glucose concentration. Guar, which has the highest viscosity when mixed with water, was also found to have the most significant effect on absorption and transit time.9 Thus, the action of guar may be twofold, depending on both delayed gastric emptying and delayed absorption of glucose in the small intestinal lumen.In our study, there were significant reductions in both the fasting plasma glucose and the one-hour postprandial plasma glucose level following guar treatment. These findings are in general agreement with those from other clinical studies.7,9,13 The mechanism responsible for these effects is not fully understood. Reduction in weight was not observed in our study as it was in others.9,10,14 Increased insulin secretion is also an unlikely explanation for the effects of guar, as no change in the levels of fasting insulin and C-peptide was observed at the beginning and end of each study phase. Indeed, Fuessl et al12 reported significant decreases in postprandial insulin and enteroglucagon responses after guar ingestion. Possible explanations for this may be improved insulin sensitivity or alteration of hepatic or peripheral glucose handling, as postulated by Jenkins et al.20Another indication of better glycemic control is the highly significant drop in the HbAl level observed during the four weeks of guar treatment. Again, this finding agrees with those reported recently and this action may well be related to delayed glucose absorption and gastric emptying.9,21 In our study, the postprandial glucose level was considerably lower after identical test meals using placebo.The effect of guar on the plasma lipid levels was significant. All patients with mean pretreatment values of total cholesterol of more than 6 mmol/L showed the most dramatic reduction; the level in some decreased to within our laboratory normal reference range (3.6-6.2 mmol/L) (Figure 1C). However, there was no significant change in the plasma triglyceride level, as was found in other studies.8,12,13,15 Moreover, recent reports have also demonstrated a reduction in the ratio of cholesterol to HDL-cholesterol; by preferential effect the guar reduced the total cholesterol but not the HDL-Cholesterol level.10,14 This would be beneficial in diabetic patients who are prone to suffer from coronary atherosclerosis, since a higher HDL:LDL ratio is believed to protect against coronary artery disease in men.22The predominant complaint of patients while on guar was soft stool, with or without frank diarrhea and flatulence, mostly present together in the same patient. Only three patients found guar inconvenient to take. Of the 33 patients with guar-induced side-effects, treatment was discontinued in only seven. In the remaining patients, the side-effects were mild, well tolerated, and abated with time. A high incidence of side-effects was also reported with placebo (beef gelatin), with symptoms similar to those seen with guar (mainly abdominal, i.e., soft stool, flatulence, and cramps). Only three patients were dropped from the study while on placebo because of intolerance. Since the side-effects decrease with continued treatment, perhaps the dose of guar should be lower initially and increased slowly over time to allow the patient to adjust to its effects.In this study of a non-Caucasoid diabetic population, we have demonstrated that the effect of guar gum is equal to that observed in studies of other ethnic groups. We therefore recommend the use of guar gum as an adjunct in the management of patients with uncontrolled NIDD on maximized conventional therapy, before switching the patient to insulin therapy.ARTICLE REFERENCES:1. Fatani HH, Mira SA, El-Zubier AG. "Prevalence of diabetes mellitus in rural Saudi Arabia" . Diabetes Care. 1987; 10(2):180–3. Google Scholar2. 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"A high carbohydrate leguminous fiber diet improves all aspects of diabetic control" . Lancet. 1981; 1:1–5. Google Scholar8. Anderson JW, Chen WL. "Plant fiber carbohydrate and lipid metabolism" . Am J Clin Nutr. 1979; 32:346–63. Google Scholar9. Jenkins DJA, Wolver TMS, Leeds AR, et al.. "Dietary fibre, fibre analogues and glucose tolerance: importance of viscosity" . Br Med J. 1978; 1:1992–4. Google Scholar10. Jenkins JW, Leeds AR, Gassull MA, et al.. "Decrease in postprandial insulin and glucagon concentrations by guar and pectin" . Ann Intern Med. 1977; 86:20–3. Google Scholar11. Jarjis HA, Blackburn NA, Redfern JS, Read NW. "The effect of ispaghule (Fybogel and metamucil) and guar gum on glucose tolerance in man" . Br J Nutr. 1984; 51:371–8. Google Scholar12. Jenkins DJA, Goff DV, Leeds AR, et al.. "Unabsorbable carbohydrates and diabetes: decreased post-prandial hyperglycaemia" . Lancet. 1976; 2:172–4. Google Scholar13. Fuessl HS, Williams G, Adrian TE, Bloom SR. "Guar sprinkled on food: effect on glycaemic control, plasma lipids and gut hormones in non-insulin-dependent diabetic patients" . Diabetic Med. 1987; 4:463–8. Google Scholar14. Aro A, Uusitupa M, Voutilainen E, et al.. "Improved diabetic control and hypocholesterolaemic effect induced by long-term dietary supplementation with guar gum in type 2 (insulin-independent) diabetes" . Diabetologia. 1981; 21:29–33. Google Scholar15. Jones DB, Lousley S, Jelfs R, et al.. "Low-dose guar improves diabetic control" . J R Soc Med. 1985; 78:546–8. Google Scholar16. Najemnik C, Kritz H, Irsigler K, et al.. "Guar and its effect on metabolic control in type 2 diabetic subjects" . Diabetes Care. 1984; 7:215–20. Google Scholar17. Fuessl HS, Adrian TE, Bacarese-Hamilton AJ, Bloom SR. "Guar in NIDD: effect on different modes of administration on plasma glucose and insulin responses to a starch meal" . Practical Diabetes. 1986; 3:258–60. Google Scholar18. Peterson DB, Mann JI. 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Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byGupta A (2019) Guar Gum in Non-Insulin Dependent Diabetes Mellitus, Annals of Saudi Medicine , 11:4, (479-479), Online publication date: 1-Jul-1991. Volume 10, Issue 5September 1990 Metrics History Accepted14 November 1989Published online1 September 1990 ACKNOWLEDGMENTWe are grateful to Norgine Limited (Oxford, U.K.) for providing the guar gum (Guarina) and placebo. We appreciate the help and effort of the nurses of the Diabetic Clinics and of Mr. Mohamed Al-Jarfan, Director of the Pharmacy, and the pharmacists at King Abdul Aziz University Hospital. We also thank Mr. Abdul Aziz Al-Salih, Director of the Department of Medical Supplies at the University Hospital in Riyadh, for his help in facilitating the importation of the drugs into the country and Bennie Campos for providing expert secretarial assistance. This study was approved by the Department of Medicine and by the College of Medicine Research Centre (CMRC), King Saud University.InformationCopyright © 1990, Annals of Saudi MedicinePDF download