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Summary
There was curiosity within the impact of assorted sorts and quantities of dietary carbohydrates and proteins on blood glucose. On the premise of our earlier information, we designed a high-protein/low-carbohydrate, weight-maintaining, nonketogenic weight-reduction plan. Its impact on glucose management in folks with untreated sort 2 diabetes was decided. We check with this as a low-biologically-available-glucose (LoBAG) weight-reduction plan. Eight males have been studied utilizing a randomized 5-week crossover design with a 5-week washout interval. The carbohydrate:protein:fats ratio of the management weight-reduction plan was 55:15:30. The check weight-reduction plan ratio was 20:30:50. Plasma and urinary β-hydroxybutyrate have been comparable on each diets. The imply 24-h built-in serum glucose on the finish of the management and LoBAG diets was 198 and 126 mg/dl, respectively. The proportion of glycohemoglobin was 9.8 ± 0.5 and seven.6 ± 0.3, respectively. It was nonetheless lowering on the finish of the LoBAG weight-reduction plan. Thus, the ultimate calculated glycohemoglobin was estimated to be ∼6.3–5.4%. Serum insulin was decreased, and plasma glucagon was elevated. Serum ldl cholesterol was unchanged. Thus, a LoBAG weight-reduction plan ingested for five weeks dramatically lowered the circulating glucose focus in folks with untreated sort 2 diabetes. Probably, this might be a patient-empowering option to ameliorate hyperglycemia with out pharmacological intervention. The long-term results of such a weight-reduction plan stay to be decided.
RESEARCH DESIGN AND METHODS – “does protein elevate blood sugar”
Males with delicate, untreated sort 2 diabetes have been studied in a particular diagnostic and remedy unit (SDTU; just like a medical analysis heart). All members met the Nationwide Diabetes Knowledge Group standards for the analysis of sort 2 diabetes (8). Participant traits are given in Desk 1. The examine was authorised by the Division of Veterans Affairs Medical Middle and the College of Minnesota Committees on Human Topics, and written knowledgeable consent was obtained from all members. The members didn’t have hematologic abnormalities, kidney illness, liver illness, macroalbuminuria (>300 mg/24 h), congestive coronary heart failure, or untreated thyroid illness. Earlier than the examine, all members have been interviewed to find out their bodily exercise profile and meals aversions and to elucidate the examine course of and dedication intimately. Contributors confirmed that that they had been weight steady for at the very least 3 months. They have been instructed to keep up their present exercise stage all through the examine. Two weeks earlier than starting the examine, the members accomplished a 3-day meals frequency questionnaire, with one of many days being a Saturday or a Sunday. This data was used to calculate the overall meals power crucial to keep up physique weight. Not one of the members have been being handled with oral hypoglycemic brokers or insulin on the time of enrollment within the examine. A 5-week randomized, crossover examine design was used with a 5-week washout interval between diets.
The management (15% protein) weight-reduction plan was designed based on the suggestions of the American Coronary heart Affiliation (9) and the U.S. Division of Agriculture (10,11). The weight-reduction plan consisted of 55% carbohydrate, with an emphasis on starch-containing meals, 15% protein, and 30% fats (10% monounsaturated, 10% polyunsaturated, and 10% saturated fatty acid). A second weight-reduction plan was designed to encompass 20% carbohydrate, 30% protein, and 50% fats. The saturated fatty acid content material of the check weight-reduction plan was ∼10% of complete meals power; thus, the vast majority of the fats was mono- and polyunsaturated. This weight-reduction plan is referred to within the textual content because the LoBAG weight-reduction plan. The composition of the diets is given in Desk 2.
Contributors have been randomized to start the examine with both the LoBAG or the management weight-reduction plan by a flip of a coin. Six members began on the LoBAG weight-reduction plan, and 5 members began on the management weight-reduction plan. Sadly, three of the members who began on the management weight-reduction plan didn’t full the examine for private causes (dying of partner, transfer throughout nation, selected to not end). Due to this fact, the info are offered on eight members who accomplished each arms of the examine. Contributors have been admitted to the SDTU on the night earlier than the examine. The following day, standardized meals that contained 55% carbohydrate, 30% fats, and 15% protein got for breakfast, lunch, and dinner at 0800, 1200, and 1800. Contributors have been requested to stay within the SDTU through the examine interval with minimal exercise.
On the second day within the SDTU, standardized meals once more got. This weight-reduction plan was comparable for each baseline research and is known as “control/pre” and “LoBAG/pre” weight-reduction plan within the figures, relying on which examine weight-reduction plan adopted the inpatient keep. Along with the meals at 0800, 1200 and 1800, snacks got at 1600 and 2100. Blood was obtained fasting at 0730, 0745, and 0800, each 15 min for the primary hour after meals, each 30 min for the following 2 h, after which hourly till the following meal. Blood was drawn at a complete of 46 time factors. After this 24-h information accumulation interval, the members have been despatched dwelling with all the crucial meals for the following 2–3 days as acceptable for the weight-reduction plan to which they have been randomized.
Contributors returned to the SDTU each 2–3 days to choose up meals and meet with the examine dietitian. At the moment, they offered a urine specimen for evaluation of creatinine and urea to find out dietary compliance. In addition they have been weighed and had blood stress, complete glycohemoglobin (tGHb), and blood glucose measured. If their physique weight decreased or elevated on two successive events, then the overall meals power of the meals was elevated or decreased as acceptable to aim to keep up weight stability all through the examine. As well as, members have been interviewed relating to dietary compliance, questions or considerations in regards to the examine, and so on. On the finish of the 5-week interval, the members once more have been admitted to the SDTU and blood was drawn as described above. Right now, the management or LoBAG meals (breakfast, lunch, dinner, and snacks) got, as acceptable.
The plasma glucose focus and β-hydroxybutyrate focus have been decided by enzymic strategies utilizing an Analox analyzer with an O2 electrode (Analox Devices, London, U.Ok.). %tGHb was measured by boronate-affinity high-performance liquid chromatography (BioRad Variant; BioRad Labs, Hercules, CA). Serum immunoreactive insulin was measured utilizing an ordinary double-antibody radioimmunoassay technique utilizing kits produced by Incstar (Stillwater, MN). Glucagon and C-peptide have been measured by radioimmunoassay utilizing kits from Linco Analysis (St. Louis, MO) and Diasorin (Stillwater, MN), respectively. NEFAs have been measured enzymically utilizing a equipment manufactured by Wako Chemical substances (Richmond, VA). Weight was decided in road garments with out footwear on a digital scale (Scalitronix, White Plains, NY). Blood stress was measured utilizing a Dinemap instrument (Critikon/Mediq, Pennsauken, NJ).
The online 24-h incremental space responses have been calculated utilizing the in a single day fasting worth as baseline. Whole 24-h space responses have been calculated utilizing zero because the baseline. Each space calculations have been finished utilizing a pc program primarily based on the trapezoid rule. Statistics have been decided utilizing Scholar’s t check for paired variates, with the Statview 512+ program (Mind Energy, Calabasas, CA) for the Macintosh pc (Apple Laptop, Cupertino, CA). P < 0.05 is the criterion for significance. Knowledge are offered because the imply ± SE.
RESULTS
The typical physique weight was 219 ± 10 lb (99 ± 4.5 kg) and 216 ± 10 lb (98 ± 4.5 kg) initially of the management and LoBAG diets, respectively (Fig. 1A). On the finish of the 5 weeks on the management weight-reduction plan, the common physique weight was 215 ± 10 lb (98 ± 4.5 kg). After 5 weeks on the LoBAG weight-reduction plan, the common weight was 212 ± 9 lb (96 ± 4.1 kg). Thus, the common physique weight decreased by 4 lb (1.8 kg) through the 5-week examine interval, no matter weight-reduction plan.
Urine ketones have been monitored twice weekly whereas members have been on the LoBAG weight-reduction plan. They have been at all times zero to hint utilizing nitroprusside impregnated Ketostix (Bayer, Elkhart, IN). Twenty-four–hour urine ketones have been an identical initially and the top of the LoBAG weight-reduction plan (196 ± 8 and 196 ± 9 μmol/l, respectively). Earlier than and after the management weight-reduction plan, they have been 187 ± 7 and 203 ± 10 μmol/l, respectively.
The imply fasting β-hydroxybutyrate focus was 225 ± 15 μmol/l after 5 weeks on the management weight-reduction plan (Fig. 1B). After 5 weeks on the LoBAG weight-reduction plan, the imply fasting focus was 236 ± 27 μmol/l. The 24-h profiles have been comparable when the members ingested both weight-reduction plan.
The imply fasting glucose focus earlier than beginning the management weight-reduction plan was 180 ± 10 mg/dl (10 ± 0.6 mmol/l; Fig. 2A). After 5 weeks on the management weight-reduction plan, the fasting glucose focus was decreased to 159 ± 11 mg/dl (8.8 ± 0.6 mmol/l), however this was not important (P = 0.66). Earlier than beginning the LoBAG weight-reduction plan, the imply fasting glucose focus was 167 ± 13 mg/dl (9.3 ± 0.7 mmol/l), just like that earlier than beginning the management weight-reduction plan (P = 0.24). After 5 weeks on the LoBAG weight-reduction plan, the fasting glucose focus was considerably decreased to 119 ± 7 mg/dl (66 ± 0.4 mmol/l; P < 0.003; Fig. 2B). The imply 24-h built-in internet glucose space responses have been comparable precontrol, pre-LoBAG, and postcontrol (681 ± 174, 731 ± 159, and 730 ± 236 mg · h · dl−1 [38 ± 9.7, 41 ± 8.8, and 41 ± 13.1 mmol · h · l−1], respectively; Fig. 2 aspect graphs, left bars). After 5 weeks on the LoBAG weight-reduction plan, the online imply 24-h built-in glucose space response was decreased by 77% (165 ± 59 mg · h · dl−1) (9.2 ± 3.3 mmol · h · l−1; P < 0.02). Whole 24-h built-in glucose space responses additionally have been comparable precontrol, pre-LoBAG, and postcontrol (4,998 ± 337, 4,746 ± 301, and 4,554 ± 347 mg · h · dl−1 [278 ± 18.7, 264 ± 16.7, and 253 ± 19.3 mmol · h · l−1], respectively; Fig. 2 aspect graphs, proper bars). The whole space response after 5 weeks on the LoBAG weight-reduction plan was decreased considerably (3,023 ± 160 mg · h · dl−1 [168 ± 8.9 mmol · h · l−1]; P < 0.0004 vs. the 5-week postcontrol and P < 0.0001 vs. pre-LoBAG). On the premise of those built-in areas, the imply glucose focus over the 24-h durations of examine was lowered from 198 to 126 mg/dl (11–7 mmol/l) after 5 weeks on the LoBAG weight-reduction plan, a 36% lower (P < 0.0001).
The imply fasting insulin concentrations earlier than and after 5 weeks on each the management and the LoBAG diets have been an identical (12 ± 2 μU/ml [72 ± 12 pmol/l]; Fig. 3). The imply 24-h built-in insulin space response above the fasting worth was comparable after the pre- and postcontrol weight-reduction plan and pre-LoBAG weight-reduction plan (534 ± 73 μU · h−1 · ml−1 [554 ± 84 μU · h−1 · ml−1]; and 530 ± 81 μU · h−1 · ml−1 [3,024 ± 438, 3,324 ± 504, and 3,180 ± 486 pmol · h · l−1], respectively; Fig. 3 aspect graphs, left bars). It was decreased at 5 weeks on the LoBAG weight-reduction plan (318 ± 39 μU · h−1 · ml−1 [1908 ± 702 pmol · h · l−1). This was a lower of 40% from the pre-LoBAG worth (P < 0.01). The imply 24-h complete built-in insulin space response decreased by 25%. The imply fasting C-peptide focus earlier than and after the management weight-reduction plan was 0.86 ± 0.08 and 0.91 ± 0.08 pg/ml. It was 0.81 ± 0.09 and 0.92 ± 0.08 earlier than and after the LoBAG weight-reduction plan (information not proven). The 24-h time course response was just like the insulin response. The online C-peptide space response was decreased by 34% after 5 weeks on the LoBAG weight-reduction plan. This was statistically important (P < 0.05). The imply %tGHb was primarily unchanged through the 5 weeks on the management weight-reduction plan (Fig. 4). A lower in tGHb was current 1 week after the establishment of the LoBAG weight-reduction plan and have become important by 3 weeks on the weight-reduction plan. On the finish of the 5-week interval, the %tGHb had decreased 22%, from 9.8 ± 0.5 to 7.6 ± 0.3% (P < 0.0007). The imply fasting glucagon concentrations have been comparable earlier than and after each the management and the LoBAG diets (95 ± 11, 91 ± 8, 91 ± 7, and 94 ± 7 pg/ml, respectively; Fig. 5). After 5 weeks on the LoBAG weight-reduction plan, the glucagon response was just like the management for the primary hour after breakfast. Subsequently, the glucagon focus was increased at each time level till 0700 the following morning, apart from one time level after dinner. Each the online and the overall glucagon space responses have been considerably elevated after the LoBAG weight-reduction plan (P < 0.05). The mean fasting NEFA concentrations were 765 ± 67, 654 ± 59, 718 ± 70, and 593 ± 50 μEq/l, before and after the control and LoBAG diets, respectively (data not shown). These differences were not statistically significant (P > 0.05). The 24-h excursions have been comparable on the management and LoBAG prediet days. When the LoBAG weight-reduction plan was ingested, the fasting NEFA was decrease and the rise after the lunch meal was attenuated, as was the lower earlier than dinner. The rise after dinner was extra speedy and reached the next focus.The imply 24-h built-in internet NEFA space responses have been −5,323 ± 1,187, −2,468 ± 693, −4,525 ± 1,660, and 80 ± 1,809 μEq · h · l−1 earlier than and after the management and LoBAG diets, respectively. The small constructive space response after the LoBAG weight-reduction plan was statistically considerably totally different in contrast with the response earlier than the LoBAG weight-reduction plan (P < 0.05). Whole areas weren't statistically totally different from each other. The imply fasting triacylglycerol concentrations have been 264 ± 36, 226 ± 32, 246 ± 27, and 149 ± 23 mg/dl earlier than and after the management and LoBAG diets, respectively (Fig. 6). The fasting triacylglycerol focus was considerably decrease after 5 weeks on the LoBAG weight-reduction plan (P < 0.05). After ingestion of both weight-reduction plan, the triacylglycerol focus elevated till ∼1200–1400, decreased at 2000–2200, elevated barely at ∼2400, and subsequently returned to the fasting worth by 0800 the following morning. The imply 24-h built-in internet triacylglycerol space response was not considerably totally different between diets. Nevertheless, the imply 24-h built-in complete space response was considerably decrease after 5 weeks on the LoBAG weight-reduction plan (P < 0.05). The whole ldl cholesterol concentrations have been 195 ± 7, 184 ± 17, 188 ± 10, and 177 ± 8 mg/dl earlier than and after the management and the LoBAG diets, respectively. The LDL ldl cholesterol concentrations have been 105 ± 9, 102 ± 2, 105 ± 7, and 110 ± 6 mg/dl earlier than and after the management and the LoBAG diets, respectively. The HDL ldl cholesterol concentrations have been 38 ± 1, 37 ± 2, 37 ± 2, and 36 ± 2 earlier than and after the management and the LoBAG diets, respectively. These complete, LDL, and HDL concentrations weren't considerably totally different between diets or earlier than and after every weight-reduction plan.
DISCUSSION
We beforehand reported {that a} weight-reduction plan wherein the protein content material was elevated from 15 to 30% of complete meals power, with a corresponding lower in carbohydrate content material, resulted in a reasonable however extremely statistically important imply lower in glycohemoglobin (8.1–7.3%) after 5 weeks on the weight-reduction plan. This was the consequence of smaller postmeal glucose will increase. The fasting glucose focus was unchanged (12).
Within the current examine, the weight-reduction plan contained the identical 30% of meals power as protein. Nevertheless, the carbohydrate content material was additional lowered from 40 to twenty% of complete meals power. The management weight-reduction plan in each research is a weight-reduction plan that’s beneficial for the overall inhabitants as a way of decreasing one’s danger for coronary coronary heart illness (9).
Within the current examine, the decrease carbohydrate weight-reduction plan not solely lowered the postmeal glucose focus but in addition significantly lowered the in a single day fasting glucose focus. It’s attention-grabbing that the 29% lower noticed within the current examine is just like the 34% lower that we noticed beforehand after a 36-h quick in folks with sort 2 diabetes (5). The general consequence was a putting lower within the 24-h built-in glucose focus (Fig. 2). As well as, the share of glycohemoglobin focus on the finish of the 5-week examine interval was decreased from a imply of 9.8 to 7.6 (Fig. 4).
The examine was designed to be 5 weeks in period as a result of 33 days had been reported to be the half-time for glycohemoglobin to achieve a brand new regular state (13). If so, then the anticipated remaining proportion of glycohemoglobin can be ∼5.4 (i.e., 2.2 × 2 = 4.4; 9.8 − 4.4 = 5.4%).
We beforehand decided that with the glycohemoglobin technique that we use, every 1% glycohemoglobin represents ∼20 mg/dl glucose built-in over a 24-h interval (14). Utilizing this data and the 24-h built-in glucose focus noticed on the finish of the 5 weeks on the LoBAG weight-reduction plan, the estimated remaining proportion of glycohemoglobin can be 6.3%. Thus, the dietary modification that we check with because the LoBAG weight-reduction plan has the potential for normalizing or practically normalizing the blood glucose in folks with delicate to reasonably extreme sort 2 diabetes. However, these outcomes needs to be thought-about to be merely a proof of idea. Solely males have been studied, and the weight-reduction plan was extremely managed and was of a comparatively brief period. Thus, the generalization of those outcomes will rely upon further longer-term research wherein each women and men and totally different age and ethnic teams are included and a larger number of meals are used. As well as, despite the fact that we tried to maintain the members’ physique weight steady, the members misplaced a imply of ∼4 lb whereas ingesting each diets.
The current information additionally recommend {that a} weight-reduction plan modification wherein the protein and the fats content material is elevated will facilitate an enchancment in glycohemoglobin by the assorted pharmacological brokers used to deal with diabetes. Nevertheless, this additionally stays to be decided.
The lower in postmeal glucose concentrations noticed can simply be defined by the smaller quantity of carbohydrate within the weight-reduction plan and thus the smaller quantity of glucose absorbed after ingestion of the meals. The rationale for the tremendously decreased fasting glucose focus is unsure however is more likely to be the consequence of a lowered retailer of glycogen and thus a lower in glycogenolysis fee (5,6,15). A priori, there isn’t any cause to suspect that the LoBAG weight-reduction plan would lead to a decreased fee of gluconeogenesis. Certainly, present proof signifies that gluconeogenesis stays fixed regardless of the quantity of carbohydrate within the weight-reduction plan (16) or of the gluconeogenic substrate equipped (15,17,18).
The LoBAG weight-reduction plan resulted in a lower in 24-h built-in insulin focus. In our earlier examine wherein the protein content material of the weight-reduction plan was elevated from 15 to 30% of complete meals power, the 24-h built-in insulin focus was barely elevated in comparison with the identical management weight-reduction plan used within the current examine (12). This was anticipated as a result of dietary protein strongly stimulates insulin secretion in folks with sort 2 diabetes (19). The lower in built-in insulin focus within the current examine undoubtedly is as a result of lowered food-derived glucose content material of the weight-reduction plan. Dietary fats doesn’t stimulate insulin secretion (20), or it facilitates a modest improve (4,21,22). Fructose (2,23) and galactose (24) ingestion additionally ends in solely a small improve in insulin focus.
The serum complete, LDL, and HDL ldl cholesterol concentrations didn’t change considerably when the fats content material of the weight-reduction plan was elevated from 30 to 50% of complete meals power. Most certainly, this was as a result of the saturated fatty acid content material was saved at 10% of power in each diets. The triglyceride focus decreased as anticipated with a discount in carbohydrate within the weight-reduction plan (25). A lower in triglyceride may need been anticipated to extend HDL ldl cholesterol (26); nevertheless, this has not been a constant discovering (27–29).
The glucagon space response elevated 2.5-fold after the LoBAG weight-reduction plan. This improve is lower than the fourfold improve that we noticed in our earlier examine (12). Nevertheless, the distinction in fold improve is due, partly, to a distinction within the response to the management diets. The online space response to the three 15% protein meals (management meals) was much less within the earlier examine in contrast with the current examine (139, 127, and 160 vs. 413, 293, and 349 pg · h · ml−1, respectively). However, the precise 24-h built-in glucagon response additionally was increased within the present examine (893 vs. 525 pg · h · ml−1).
In abstract, a LoBAG weight-reduction plan can dramatically scale back the 24-h built-in glucose focus and consequently the share of glycohemoglobin in folks with sort 2 diabetes. These constructive outcomes happen with no important change in serum lipids, apart from a big lower in triacylglycerol focus.
“does protein elevate blood sugar”