Should we advice diabetic and obese patients to stop eating breakfast?

02 February 2014 20 8K Report

They are insulin resistant on waking up and eating cho/fat/balanced breakfast worsens their post prandial surge of glucose that accumulates throughout the day.

Matthew Bowen Popular answer

Here is a little piece I wrote up about diurnal variations, meal timing, and meal frequency in DM2. Would love to hear feedback.

In the memoirs of Dr. George Cahill (32) entitled “Fuel Metabolism in Starvation”, which summarized a lifetime of medical research on starvation, fasting and diabetes, Dr. Cahill notes:

“We also fasted two type 2 diabetics, who differed from the normals by better nitrogen conservation. They were slightly more efﬁcient, in keeping with the concept of James Neel (at Michigan) that type 2 diabetes may have been an evolutionary selective advantage in a starving population”.

These results were subsequently supported, in that those with DM2 produced more ketones in response to starvation, indicating that they were indeed more efficient at producing the most energy-dense and efficient fuel currency suitable for starvation (33). Fairman & Moorhouse (33) also noticed a significant diurnal rhythm under fasting conditions now commonly referred to as “The Dawn Phenomenon”, which results in a dramatic increase in fasted morning glucose levels. The Dawn Phenomenon has since been observed in studies on individuals with DM2 (34). Many researchers attribute this phenomenon to the morning increase in cortisol - unsurprisingly the administration of the cortisol inhibitor Metyrapone resulted in a decrease of plasma cortisol and blood glucose during a 12h fasted morning test in those with DM2 (35), and hyperglycemia is routinely observed in those who suffer from hypercortisolism (36). It has also been observed that lean patients with DM2 and glucose intolerance had an enhanced sensitivity to cortisol, which contributed significantly to hyperglycemia (37). Although healthy non-diabetic individuals experience a morning increase in cortisol, and young healthy (opposed to healthy elderly) non-diabetic individuals experience a morning increase in blood glucose levels (38), this is attenuated by an increase in insulin secretion which is not observed in those with DM2 (39). It has been observed that cortisol administration suppresses peripheral and hepatic insulin sensitivity, even in healthy individuals (40). These observations on endogenous cortisol levels and metabolic response to fasting in DM2 population beg the question: does time of day affect the glucose response to a meal, and what else may be a contributing factor?

It has been routinely observed that healthy individuals are most insulin sensitive in the morning (41), when fed breakfast (42), and perform the poorest at night in an oral glucose tolerance test (41, 43) - although randomized control trials testing breakfast inclusion or omission have had mixed results (44). The only experiment accounting for calorie intake and assessing this in DM2 demonstrated the benefits of delaying the majority of caloric intake to the evening – when 70% of daily calories were consumed after 1900h, 24h insulin secretion and serum glucose were decreased, insulin sensitivity was greater in response to a meal, and no abnormal elevation in night time and morning glucose was observed the subsequent day (45). Importantly, individuals with DM2 studied under hyperglycemic clamp showed a very clear diurnal rhythm whereby insulin sensitivity reached peak at 7PM, and a nadir in the morning at 8AM – insulin sensitivity was inversely related to measures of cortisol and free fatty acid, which both showed clear diurnal rhythms as well (46). Additionally, it was shown that a snacking meal pattern (3 meals + 3 snacks a day) led to greater mean 24h serum glucose when compared to less frequent (3 meals per day) meal intake (34) – yet 3 meals with snacks is the first line recommendation from the Canadian Diabetes Association for the management of glucose levels.(47) A previous trial has demonstrated the difficulty of managing morning hyperglycemia in individuals with DM2. It was shown that the largest glucose excursions occurred in between the time of breakfast and lunch in individuals with DM2 irrespective of BMI, HOMA, HbA1c, and B-cell function (48). These striking observations highlight that alternative meal timing strategies have the potential to greatly influence glucose levels and in turn impact the development of the chronic complications of DM2 over that of the currently recommended dietary strategy in DM2 management.

1.5.2 Intermittent Fasting in Healthy Individuals and Individuals with DM2

One simple dietary intervention is Intermittent Fasting (IF), whereby caloric intake is restricted to a specific window of time followed by feeding within a restricted window of time. There are many variations of IF, however, of interest is a particular popularized practice whereby an individual restricts caloric intake for 18 to 20 hours per day (unrestricted zero-calorie water, coffee and tea intake permitted during this time), followed by ad libitum feeding during midday or evening for 4-6 hours with an emphasis on a high protein intake to promote satiety. This version of IF is particularly interesting because meal intake occurs during the periods of time when those with DM2 reach a diurnal peak in insulin sensitivity, and fasting occurs when cortisol and free fatty acids are at their diurnal peaks. Similar protocols (with the exception of no increase in dietary protein intake, which will be discussed in following sections) have been studied (49-52) in non-diabetic populations with beneficial effects on insulin-mediated glucose uptake, insulin inhibition of lipolysis, reduction of basal cortisol levels, loss of body fat, and increases in the anti-diabetic hormone adiponectin – all in the absence of caloric restriction or weight loss. Two of these studies (50, 51) noticed a significant drop in fasting morning cortisol, a change not typically seen during a change in dietary patterns – and this has relevance in DM2 since morning levels in cortisol contribute significantly to fasting hyperglycemia (34). In fact, dieting most often promotes an elevation in cortisol (19) making these results all the more unique. Also, in calorie controlled circumstances, the biggest complaint from participants was that they felt too full when trying to consume an entire day’s worth of calories in the 4 hour feeding window, so much so that participants still lost a marginal amount of weight despite active encouragement from staff to eat more (50, 51). This lends credibility to the hypothesis that IF would create a spontaneous caloric deficit in free living conditions when practiced consistently, a necessity for the reversal of DM2 (4).

Recently, IF has been gaining attention in popular media and the medical community for its potential therapeutic use in the treatment and prevention of cardiovascular disease and DM2 (53). However, only a single trial has looked at the acute effects of IF in individuals with DM2. This trial compared the effects of three dietary intake patterns (low-fat and low-carbohydrate breakfast + lunch and a Mediterranean-style lunch without breakfast) with a randomized cross-over design on postprandial glucose, insulin, triglycerides and gastric inhibitory polypeptide (GIP) in individuals with DM2 (54). The Mediterranean lunch, despite doubling the calorie content of the low-fat and low-carbohydrate lunches (equaling the total caloric intake of the breakfast + lunch in low-fat and low-carbohydrate conditions), had equivalent glucose and insulin excursions as the low-fat lunch, equivalent triglyceride excursions compared to the low-carbohydrate and low-fat lunches, and increased and extended GIP excursions compared to both the low-fat and low-carbohydrate lunches. The Mediterranean lunch without breakfast also had the added benefit of no increase in glucose, insulin, or triglycerides during the breakfast period (despite coffee intake), which all significantly increased above baseline during the low-fat and low-carbohydrate breakfasts. There were several confounding variables in this trial that the authors admitted to in the discussion of the paper, but regardless, this serves as interesting pilot data that should lead to further research of intermittent fasting in DM2.

32. Cahill Jr GF. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1-22.

33. Faiman C, Moorhouse JA. Diurnal variation in the levels of glucose and related substances in healthy and diabetic subjects during starvation. Clin Sci. 1967 Feb;32(1):111-26.

34. Bolli GB, Gerich JE. The dawn Phenomenon—A common occurrence in both non-insulin-dependent and insulin-dependent diabetes mellitus. N Engl J Med. 1984;310(12):746-50.

35. Atiea JA, Aslan SM, Owens DR, Luzio S. Early morning hyperglycaemia "dawn phenomenon" in non-insulin dependent diabetes mellitus (NIDDM): Effects of cortisol suppression by metyrapone. Diabetes Res. 1990 Aug;14(4):181-5.

36. Friedman TC, Mastorakos G, Newman TD, Mullen NM, Horton EG, Costello R, et al. Carbohydrate and lipid metabolism in endogenous hypercortisolism: Shared features with metabolic syndrome X and NIDDM. Endocr J. 1996 Dec;43(6):645-55.

37. Andrews RC, Herlihy O, Livingstone DE, Andrew R, Walker BR. Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. Journal of Clinical Endocrinology & Metabolism. 2002;87(12):5587-93.

38. Rosenthal MJ, Argoud GM. Absence of the dawn glucose rise in nondiabetic men compared by age. J Gerontol. 1989 Mar;44(2):M57-61.

39. SHAPIRO ET, POLONSKY KS, COPINSCHI G, BOSSON D, TILLIL H, BLACKMAN J, et al. Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes*. The Journal of Clinical Endocrinology & Metabolism. 1991;72(2):444-54.

40. Rizza RA, Mandarino LJ, Gerich JE. Cortisol-induced insulin resistance in man: Impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action*. The Journal of Clinical Endocrinology & Metabolism. 1982;54(1):131-8.

41. Bowen AJ, Reeves RL. Diurnal variation in glucose tolerance. Arch Intern Med. 1967 Mar;119(3):261-4.

42. Svanfeldt M, Thorell A, Hausel J, Soop M, Nygren J, Ljungqvist O. Effect of “preoperative” oral carbohydrate treatment on insulin action—a randomised cross-over unblinded study in healthy subjects. Clinical Nutrition. 2005;24(5):815-21.

43. Jarrett RJ, Baker IA, Keen H, Oakley NW. Diurnal variation in oral glucose tolerance: Blood sugar and plasma insulin levels morning, afternoon, and evening. Br Med J. 1972 Jan 22;1(5794):199-201.

44. Timlin MT, Pereira MA. Breakfast frequency and quality in the etiology of adult obesity and chronic diseases. Nutr Rev. 2007;65(6):268-81.

45. Beebe CA, Van Cauter E, Shapiro ET, Tillil H, Lyons R, Rubenstein AH, et al. Effect of temporal distribution of calories on diurnal patterns of glucose levels and insulin secretion in NIDDM. Diabetes Care. 1990 Jul;13(7):748-55.

46. Boden G, Chen X, Urbain JL. Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production. Diabetes. 1996 Aug;45(8):1044-50.

47. Just the basics [Internet].: Canadian Diabetes Association; 2010; cited Oct. 13 2013]. Available from: http://www.diabetes.ca/files/JTB17x_11_CPGO3_1103.pdf.

48. Monnier L, Colette C, Rabasa-Lhoret R, Lapinski H, Caubel C, Avignon A, et al. Morning hyperglycemic excursions: A constant failure in the metabolic control of non-insulin-using patients with type 2 diabetes. Diabetes Care. 2002 Apr;25(4):737-41.

49. Halberg N, Henriksen M, Söderhamn N, Stallknecht B, Ploug T, Schjerling P, et al. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol. 2005;99(6):2128-36.

50. Stote KS, Baer DJ, Spears K, Paul DR, Harris GK, Rumpler WV, et al. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Am J Clin Nutr. 2007;85(4):981-8.

51. Carlson O, Martin B, Stote KS, Golden E, Maudsley S, Najjar SS, et al. Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. Metab Clin Exp. 2007;56(12):1729-34.

52. Soeters MR, Lammers NM, Dubbelhuis PF, Ackermans M, Jonkers-Schuitema CF, Fliers E, et al. Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism. Am J Clin Nutr. 2009;90(5):1244-51.

53. Brown JE, Mosley M, Aldred S. Intermittent fasting: A dietary intervention for prevention of diabetes and cardiovascular disease? The British Journal of Diabetes & Vascular Disease. 2013;13(2):68-72.

54. Fernemark H, Jaredsson C, Bunjaku B, Rosenqvist U, Nystrom FH, Guldbrand H. A randomized cross-over trial of the postprandial effects of three different diets in patients with type 2 diabetes. PloS one. 2013;8(11):e79324.

Constantine Kaniklidis

Kaz:

Although the reasoning may sound intuitive, even compelling, in fact I have found in review [27] that just the opposite is the case, and below I provide a summary of the evidence on the protective and preventive benefit of consistent breakfast consumption on metabolic disease:

THE PROTECTIVE AND PREVENTIVE EFFECT OF DAILY BREAKFAST CONSUMPTION ON METABOLIC DISEASE (OBESITY/DIABETES)

Breakfast-omission behavior is one of many well-documented dietary factors playing a critical role in the etiology of obesity, as found in the extensive NHANES data [1], and furthermore there is overwhelming evidence of a strong association between breakfast-omission the rise in obesity, as shown in the Project EAT (Eating Among Teens) study [4], the National Heart, Lung, and Blood Institute NGHS (Growth and Health Study) [7] and numerous others in confirmation [2,3,5,6]., with over the past two decades the significant substantial decline in breakfast consumption closely paralleling the rise in obesity [2-7].

The association, and the fact of breakfast-omission as a critical dietary factor in the etiology of obesity, is mediated in part via the evidenced inverse, dose-dependent association between breakfast frequency and BMI (the smaller the incidence of breakfast eating occasions, the greater the increases in BMI [4,8,9]), and we know that breakfast-omission is twice as likely among the overweight and obese young than their normal-weight counterparts [9,10], and those who engage in breast-omission behavior furthermore have an increased prevalence of being obese and have higher BMI percentiles and z scores compared with regular breakfast consumer [1,9]. This is consonant with the findings of NWCR (the National Weight Control Registry [11], which has followed over 5000 individuals who have succeeded at significant weight loss (at least 13.6 kg for at least 1 year), to identify the key characteristics of such success, finding that the vast majority (78%) are regular daily breakfast consumers, with only 4% being breakfast-omitters, indicative of a strong positive protective effect of consistent daily breakfast consumption for the prevention of weight gain and obesity (and diabetes; see below).

Besides the etiological mediation with BMI, another key mediator of this positive association is that of glucose and insulin metabolism. Thus, one study [12] documented the adverse effects of of breakfast-omission on insulin sensitivity and fasting lipid profiles in healthy lean women: breakfast-omission led to greater daily energy intake versus eating breakfast, amazingly despite an additional 500 kcal consumed with breakfast, and the breakfast-omitters had higher fasting total cholesterol as well as LDL cholesterol along with reduced insulin sensitivity to a test breakfast meal compared with breakfast consumers, further confirmed in another study [13] where it was found that it was breakfast-omission, as opposed to the consumption a 650-kcal breakfast, that led to compromised glucose control at the following meal, accompanied by a much larger rise in plasma glucose in response to a standardized lunch meal compared with when breakfast was consumed. Additional data from the landmark University of Minnesota study [14] found that the addition of a 500-kcal breakfast was consistently and strongly associated with significant postbreakfast reductions in perceived appetite, along with increases in both perceived fullness and in the satiety hormone PYY (peptide YY), with a concomitant reduction in energy intake at lunch.

These conclusions are also in agreement with an American Society of Nutrition (ASN) hosted symposium entitled “Eating Patterns and Energy Balance: A Look at Eating Frequency, Snacking, and Breakfast Omission” at the Experimental Biology 2009 annual meeting (19 April, 2009, New Orleans, LA) [].

And note that these findings have been replicated across numerous cultures, geographies and ethnic groups. I myself have reviewed this issue for India (summary of findings previously posted on ResearchGate), where a cross-sectional study [16] in Delhi found that daily breakfast consumption is associated with healthier dietary- and physical activity-related behaviors and lower incidence of overweight and obesity among urban Indian students, with the combined prevalence of overweight and obesity among school-going adolescents (12–18 years) in Delhi being 16.6% [17]. So although the etiology of childhood obesity is soberingly complex and massively multi-factorial across a spectrum of behavioral, intra-personal, and social-environmental risk and countervailing protective factors, one in particular has been found to be critical in India, namely the consumption of breakfast. Thus, another landmark study [18] found that daily breakfast intake was associated with a lower likelihood of overweight and obesity among urban Indian adolescents and in strictly a dose-dependent manner, with regular breakfast consumers significantly less overweight and obese compared to (sporadic) breakfast-skippers, who, in turn were significantly less overweight and obese than never-breakfast consumers, once again attributing a strong protective deriving from regular breakfast consumption in the prevention and/or treatment obesity/type 2 diabetes. I have found comparable and confirmative results in my review of the same issues in the Middle East, across Arab nations, Iran and Israel alike.

CONCLUSIONS

The elevated diabetes risk association with breakfast omission is at least as strong evidentiarily than that with obesity: thus in several large prospective cohort studies, irregular breakfast consumption was associated with a significantly higher risk of diabetes and breakfast consumption was associated with significantly lowered diabetes risk, in women [19] as well as men [20] in the Health Professionals Follow-Up Study (HPFS) and others, and also, independently demonstrated in the CHASE (Child Heart and Health Study in England) Study [24] for a n a multiethnic population of children. This was found to be independent of indicators of dietary quality or BMI [19,20], cross-confirmed in another long-term prospective study not just for diabetes but for a wide spectrum of metabolic dysfunctions including abdominal obesity, general obesity, metabolic syndrome, as well as hypertension [21], and also coronary heart disease [23], and again it must be noted, with no evidence of differential results for high versus low overall dietary quality [21]. Moreover, in a study of the differential effects of high caloric intake at breakfast vs. at dinner [22], fasting glucose, insulin, and HOMA-IR were all decreased significantly to a greater extent in the breakfast group, suggesting that high-calorie breakfast with reduced intake at dinner can play an important role the management of obesity and metabolic syndrome.

Thus although there still remain some methodological issues of concern that require further study and debate [26; repsonse:27] the cumulative evidence [1-25] to date shows that regular breakfast consumption is significantly reductive of (especially in the young), and reductive of risk of a broad spectrum factors contributing to metabolic syndrome / obesity / diabetes, as well as other metabolic dysfunctions including hypertension [21], and also coronary heart disease [23] making breakfast consumption a key preventive component against obesity and diabetes, particularly among the young.

METHODOLOGY OF THE REVIEW

A search of the PUBMED, Cochrane Library / Cochrane Register of Controlled Trials, MEDLINE, EMBASE, AMED (Allied and Complimentary Medicine Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, ISI Web of Science (WoS), BIOSIS, LILACS (Latin American and Caribbean Health Sciences Literature), ASSIA (Applied Social Sciences Index and Abstracts), SCEH (NHS Evidence Specialist Collection for Ethnicity and Health) and SCIRUS databases was conducted without language or date restrictions, and updated again current as of date of publication, with systematic reviews and meta-analyses extracted separately. Search was expanded in parallel to include just-in-time (JIT) medical feed sources as returned from Terkko (provided by the National Library of Health Sciences - Terkko at the University of Helsinki). A further "broad-spectrum" science search using SCIRUS (410+ million entry database) was then deployed for resources not otherwise included. Unpublished studies were located via contextual search, and relevant dissertations were located via NTLTD (Networked Digital Library of Theses and Dissertations) and OpenThesis. Sources in languages foreign to this reviewer were translated by language translation software.

REFERENCES

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2. Rampersaud G. Breakfast habits, nutritional status, body weight, and academic performance in children and adolescents. J Am Diet Assoc. 2005;105:743-760.

3. Mesas AE, Muñoz-Pareja M, López-García E, Rodríguez-Artalejo F. Selected eating behaviours and excess body weight: a systematic review. Obes Rev. 2012;13:106-135.

4. Timlin M. Breakfast eating and weight change in a 5-year prospective analysis of adolescents: Project EAT (Eating Among Teens). Pediatrics. 2008;121:e638-e645.

5. Giovannini M, Verduci E, Scaglioni S, et al. Breakfast: a good habit, not a repetitive custom. J Int Med Res. 2008;36:613-624.

6. Niemeier HM, Raynor HA, Lloyd-Richardson EE, Rogers ML, Wing RR. Fast food consumption and breakfast skipping: predictors of weight gain from adolescence to adulthood in a nationally representative sample. J Adolesc Health. 2006;39:842-849.

7. Barton BA, Eldridge AL, Thompson D, et al. The relationship of breakfast and cereal consumption to nutrient intake and body mass index: the National Heart, Lung, and Blood Institute Growth and Health Study. J Am Diet Assoc. 2005;105:1383-1389.

8. Mesas AE, Muñoz-Pareja M, López-García E, Rodríguez-Artalejo F. Selected eating behaviours and excess body weight: a systematic review. Obes Rev. 2012;13:106-135.

9. Siega-Riz AM, Popkin BM, Carson T. Trends in breakfast consumption for children in the United States from 1965-1991. Am J Clin Nutr. 1998;67:748S-756S.

10. Keski-Rahkonen A, Kaprio J, Rissanen A, Virkkunen M, Rose RJ. Breakfast skipping and health-compromising behaviors in adolescents and adults. Eur J Clin Nutr. 2003;57:842-853.

11. Wyatt HR, Grunwald GK, Mosca CL, Klem ML, Wing RR, Hill JO. Long-term weight loss and breakfast in subjects in the National Weight Control Registry. Obes Res. 2002;10:78-82.

12. Farshchi HR, Taylor MA, Macdonald IA. Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women. Am J Clin Nutr. 2005;81:388-396.

13. Jovanovic A, Gerrard J, Taylor R. The second-meal phenomenon in type 2 diabetes. Diabetes Care. 2009;32:1199-1201.

14. Pereira MA, Erickson E, McKee P, et al. Breakfast frequency and quality may affect glycemia and appetite in adults and children. J Nutr. 2011;141:163-168.

15. Leidy HJ. The Benefits of Breakfast Consumption to Combat Obesity and Diabetes in Young People. Am J Lifestyle Med March/April 2013; 7(2):99-103.

16. Arora M, Nazar GP, Gupta VK, Perry CL, Reddy KS, Stigler MH. Association of breakfast intake with obesity, dietary and physical activity behavior among urban school-aged adolescents in Delhi, India: results of a cross-sectional study. BMC Public Health. 2012 Oct 17;12:881.

17. Stigler MH, Arora M, Dhavan P, Shrivastav R, Reddy KS, Perry CL: Weight-related concerns and weight-control behaviors among overweight adolescents in Delhi, India: A cross-sectional study. Int J Behav Nutr Phys Act 2011, 8:9-14.

18. Arora M, Nazar GP, Gupta VK, Perry CL, Reddy KS, Stigler MH. Association of breakfast intake with obesity, dietary and physical activity behavior among urban school-aged adolescents in Delhi, India: results of a cross-sectional study. BMC Public Health. 2012 Oct 17;12:881.

19. Mekary RA, Giovannucci E, Cahill L, Willett WC, van Dam RM, Hu FB. Eating patterns and type 2 diabetes risk in older women: breakfast consumption and eating frequency. Am J Clin Nutr 2013; 98(2):436-43.

20. Mekary RA, Giovannucci E, Willett WC, van Dam RM, Hu FB. Eating patterns and type 2 diabetes risk in men: breakfast omission, eating frequency, and snacking. Am J Clin Nutr 2012; 95(5):1182-9.

21. Odegaard AO, Jacobs DR, Steffen LM, Van Horn L, Ludwig DS, Pereira MA. Breakfast frequency and development of metabolic risk. Diabetes Care 2013; 36(10):3100-6.

22. Jakubowicz D, Barnea M, Wainstein J, Froy O. High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring) 2013; 21(12):2504-12.

23. Cahill LE, Chiuve SE, Mekary RA, et al. Prospective Study of Breakfast Eating and Incident Coronary Heart Disease in a Cohort of Male US Health Professionals. Circulation. 2013; 128: 337-343.

24. Donin AS, Nightingale CM, Owen CG, et al. 8Not Eating Breakfast is Associated with increased Type 2 Diabetes Risk Markers in a Multiethnic Population of Children: the Child Heart and Health Study in England (CHASE). J Epidemiol Community Health 2013;67:A3.

25. McCrory MA, Campbell WW. Effects of eating frequency, snacking, and breakfast skipping on energy regulation: symposium overview. J Nutr. 2011 Jan;141(1):144-7.

26. Brown AW, Bohan Brown MM, Allison DB. Belief beyond the evidence: using the proposed effect of breakfast on obesity to show 2 practices that distort scientific evidence. Am J Clin Nutr 2013; 98(5):1298-308.

27. Mekary RA, Giovannucci E. Belief beyond the evidence: using the proposed effect of breakfast on obesity to show 2 practices that distort scientific evidence. [Letter] Am J Clin Nutr 2014; 99(1):212-3.[Response to Brown et al., Am J Clin Nutr 2013]

27. Kaniklidis, C. Daily Breakfast Consumption Exerts Protective And Preventive Effects On Metabolic Disease (Obesity/Diabetes): A Review. [2014; publication pending].

Salih Sanlioglu

From what I have read, omitting breakfast is not a good habit from obesity and diabetes perspective..Omitting dinner might do some good in losing weight though..

Matthew Bowen

We are currently under way in a trial testing the effects of Intermittent Fasting (omitting breakfast and delaying lunch) in individuals with Type 2 diabetes. Our rationale is that large meals in the morning account for the largest bouts of hyperglycemia, and that people with DM2 have pretty clear diurnal rhythms, whereby insulin sensitivity is at nadir in the morning and peaks in the late afternoon and evening. We've ran five people through the study so far, and results have been predominantly positive, particularly for individuals who delay meal intake to the late afternoon (most notable were the improvements in CRP, FPG and random glucose).

I would also like to clarify that the research on breakfast omission/inclusion at this point is very weak, and has rarely been tested in controlled experiments with obese people, and never with DM2 (it is very important to note that healthy lean individuals are completely different - apples and oranges). At this point most of the conclusions on breakfast have been drawn from survey data, which only gives us associations rather than causality. More controlled experiments need to be done at this point.

Kaz Mawji

Individualisation in diabetes treatment is finally here. Each diabetic has a trend that reflects their metabolic rate. I hypothiese that it is reflected in their fasting cortisol (saliva): insulin ratio. (Yet to be scientifically verified). However "an elevated blood F/E ratio in patients with type 2 diabetes has been reported (Valsamakis et al.,2004, Homma et al.,2001, Sinha & Caro 1998)." It's this that defines glucose AUC. At its nadir can the diabetics/obese/normal/metabolic syndrome clients safely eat their first meal of the day, and not fearing that their incretins will lag behind and cause glycogen storage. sure look at HOMA-IR etc. This is important to define so to enable us to advice diabetics/obese/MS clients regarding ways of adopting healthy life style. Matthew, significant number (bias!) who will show this trend. We are finally bulking the same myth that griped us tight about one size fits all. I truly look forward to the outcome of your work. Plz keeping posting interim results.

Julie M. Kittelsrud

I have to agree with Constantine Kaniklidis. It can be typical to see glucose surges in the morning for diabetic patients. These surges are related to hormonal fluctuations and regular circadian changes throughout the day/night cycle. Omitting breakfast is not recommended for weight reduction, nor would I recommend it for type 2 diabetes. I would suggest a modified carbohydrate load, meaning reduce carbohydrate load at night and then for breakfast. Furthermore, adjustments could be made with medications to take into consideration the peak action of the medication. The peak action of the medications should occur at the time the patient tends to spike glucoses (for many this is early morning). THis will normalized the glucoses throughout the day and perhaps help with controlling hunger related to hyper or hypoglycemia.

With that said though, Mathew Bowen, I'd be interested to see the results of your study. It is an intreging thought to abstain from breakfast until later. I would assume that you are standardizing the meal, and testing insulin levels, glucose levels, grehlin. letptin etc...???

Matthew Bowen

Results will not be published until late 2015, Julie. We are testing a commonly practiced version of Intermittent Fasting in free-living individuals with DM2 over a period of a month (and gauging before/after effects) - our main outcomes are biochemical changes in common clinical measurements (hsCRP, FPG, insulin, HOMA-IR, lipids, BP, weight, waist circumference, self-monitored glucose) and potentially some non-standard measurements in patients depending on the availability of baseline data in people with DM2 (interleukins and other inflammatory parameters are not well researched in DM2). We are not testing grehlin or leptin, as funding is limited and most biochemical work is being done through publicly provided services.

Applying this intervention and interpreting the results can be very difficult, as there is little literature on the 24-h changes in adipokines, lipids, and inflammatory parameters with shifting and restricting meal intake, increasing acute caloric intake 12h before fasted serum test, and how these conflict with light exposure and natural diurnal rhythms. We are hoping that the results of this trial can be used to acquire funding for basic science (as doing 24-h serum measurements of non-standard biochemical markers can be very expensive).

For example, One trial that assessed the effects of IF (http://ajcn.nutrition.org/content/85/4/981.full) showed that it decreased morning cortisol concentrations during a snapshot A.K.A a single fasted serum draw - but whether or not cortisol peaks and 24-h cortisol are simply delayed or *actually* reduced by practicing IF are still unknown. Like I said before, basic science into the 24-h effects of IF/delayed meal intake needs to be done before we can draw any real conclusions on its effectiveness. The single trial we are running will likely not be able to answer that question alone.

Constantine Kaniklidis

I too welcome the pending results of the Intermittent Fasting clinical trial Matthew Bowen, above, briefly discusses, and he is to be commended for his candor about limitations, and with preliminary data on only 5 patients, as yet unreported, it is I think we would agree too early to draw conclusions. In addition, the trial is substantially tangential to the question at hand of the adverse or positive metabolic effects of breakfast-omission, since it is examining Intermittent Fasting, which as Matthew clarifies, is the omission of breakfast AND lunch postponement/displacement, and this is not the same thing as breakfast-omission: an answer to one is not necessarily an answer to the other, and moreover constrained trial duration would disallow correlatively determining durable cardiovascular sequelae such as the adverse impact on coronary heart disease (CHD) [my reference 23, above].

Indeed, no one trial as Matthew shrewdly credits, is likely to be dispositive of the issue, and we may need the collective results of the Intermittent Fasting trial, the Tel Aviv Postprandial Glucose, Insulin and GLP-1 Meal Timing T2DM Trial (NCT01977833), the Wolfson Medical Center Breakfast Size / Hormonal Profile T2DM Trial (NCT01178723), and others (one of which I am assisting in designing), along with the more robust findings of large prospective studies, to begin to clarify the complex skein of factors, pathways and effects, once we learn to control for the wide spectrum of methodological confounders. In the meantime, we have no credible evidence of a clinically relevant benefit deriving from breakfast-omission (not even in weight control) - and none has been cited or offered here - and the balance of evidence as I marshaled, albeit and admittedly provisional (As I teach in my evidence-based medicine classes, following the time-honored EBM prescripts, in the absence of the BEST OF EVIDENCE on a clinical question, we must found decisions on the balance of the BEST EVIDENCE we have to date), remains weighted against breakfast-omission until, and if, such time as more mature randomized controlled data arrives, for which I eagerly await.

Roberto Conti

I wonder why has not been mentioned the effect of drugs on Intermittent fasting. It is largely known that in type II diabetes more than 50% of morning hyperglycemia is sustained by gluconeogenesis which became prevalent as fasting goes on and glycogen disappear. Of course, if fasting is prolonged until 3:00 pm a decrease in glycemia is expected and probably also a slight, probably temporary, increase in insulin sensitivity which I think is the main end-point of a clinical trial based on IF. But what happens at lunch and dinner? I wonder if another clinical trial wil tell us if insulin sensitivity is negatively affected at night.!! This is not a diet but just a repositioning of calories. Calories repositioning may work in country like Italy were, in 70% of people, the average morning calories intake is around 300-400 Kcal (cappuccino and cornetto) very high in simple carbohydrates and so, very high glycemic index. But in US, breakfast is much more than 1000 Kcal, a complete meal. So, think to reposition these 1000 Kcal, 500 at lunch and 500 at dinner.

Any nutritionist in the world claims that at dinner we need to be light !!

Moreover, since the diabetic patients are on treatment, does really IF could give an advantage? In Italy, for instance, the majority of type II diabetes patients are still treated with the combo sulfonilureas/metfomin which easily give hypoglycemia in the morning and they need a breakfast. But in terms of treatment, the worst is the increase of calories at lunch and dinner which, of course, will require a more aggressive dosage.

As many post on this discussion, I agree with the one suggesting to always check daily calories intake (nobody does in Italy) eating complex carbohydrates at breakfast (better always). In US, less calories at breakfast and more at lunch in a relaxed place (slow food). On the contrary, in Italy more calories at breakfast with complex carb and less food in general...(we eat too much)

Regards.

Kaz Mawji

Constantine:

Are the "the Wolfson Medical Center Breakfast Size / Hormonal Profile T2DM Trial (NCT01178723)," , weighing the breasfast for calorie content?. My apologies I cannot get into their methodology. It would have brilliant if they had also included "Hand Portion diet" as on of their arms. This is individualised caloric intake method.

Wasiu Gbolahan Balogun

as some colleague have said, the breakfast is not the problem, obese people should be advice to either delay breakfast till later in the day like noon or take food with little calorie. they should be advice strongly to drop the dinner which is the food of fear in obese and DM patients.

Constantine Kaniklidis

Kaz:

Individualized caloric content is something of a Holy Grail in diabetes meal fasting/timing trials but generally has been beyond the protocol control of existing trials. Outside of epidemiological/observational studies which are perforce at the individualized level of study, controlled trials cannot realistically incorporated individualized meal content. So, in general, some trials control general-level meal composition and caloric distribution within prescribed limits to allow for the legitimacy of intervention-to-control-arm comparisons, but typically not person-to-person variation. So for example in the randomized crossover USDA/BHNRC/NIA trial Matthew referred to above all meals were dietitian-supervised and precisely content-constrained by the trial sponsors.

Roberto:

You raise some important points that I will only briefly comment on. Endogenous glucose production (EGP), glycogenolysis and gluconeogenesis are contributors to fasting morning hyperglycemia, and the cyclicity of these processes is autonomous, occurring independently of the exogenous influence of meals, and as demonstrated in the Ottawa study (Radziuk & Pye, Diabetologia 2006), glucose concentrations in diabetics but not nondiabetcs exhibits strong and spontaneous circadian rhythm driven diurnal variation spanning a gradual transition from a late evening nadir to a morning peak, these phenomena themselves apparently highly melatonin-dependent. Increasing evidence suggests a central role in glucose homeostasis and diabetes etiology and pathology (melatonin levels are consistently lower in diabetic compared to nondiabetic patients, and diabetes appears to be associated with sleep disruptions even in the absence of complications or obesity), with significant reduction in HbA1c in type 2 diabetic patients on long-term low-dose (~2 mg) melatonin therapy [results of the Tel Aviv University/Wolfson Medical Center randomized, double-blind crossover trial (Diabetes Metab Syndr Obes. 2011)], and unsurprisingly we have provisional data that melatonin can enhance glycemic control in adult diabetics (Grieco et al, International Journal of Diabetes Research 2013; among many others), allowing for the postulation of a tight insulin-melatonin nexus and also suggesting that blocking melatonin-induced inhibition of insulin secretion is likely to be a novel therapeutic target in adult T2DM, especially via agents that target the melatonin receptors (MT1 and, especially MT2 and its mutations, according to recent genome-wide association studies). Results from further trials, including the IF trail Matthew above is involved in, may help clarify this further, and help integrate the complex relationships between

- intermittent fasting (IF) and intermittent energy/caloric restriction (EER or ICR) both of which appear to reduce insulin resistance (and with preliminary data of an anticancer benefit via, I note, favorable modulation of the IGF insulin and MTOR molecular pathways),

-postprandial hyperglycemia,

- the infamous Dawn phenomenon (the night-to-early-morning elevation of blood glucose (BG)),

- sleep dysfunctions in diabetics,

- the interaction of statin therapy and diabetes (whether there are clinically relevant deleterious hyperinsulinemic and diabetogenic effects and the impact on outcomes, as well as the differential effects of statin type and dosing)

and other challenges in the underlying dynamics of diabetes, although given the present scarcity of robust clinical trials, it pays to be properly circumspect as Matthew suggests in his important posting above (see his comments especially on the complexities of discovering and tracking diurnal variation markers) before both basic science explorations, and human clinical trials (which must be informed by the basic science that remains limited) can advance the state of the field.

And yes, there may indeed be cultural and ethnic variations that need be studied (the works of Kim Stote and colleagues at USDA and Caleb Kelly at Tufts bring up intriguing variations across American, Ramadan-fasting Muslims, and Seventh-day Adventists), and these need to be further explored along with the consequences of the associated dietary patterns.

Balogun:

Investigators are still untangling the role of specific meals and their omission, complicated given some of the issue of diurnal and circadian variation briefly mentioned above, but we should know more as more robust studies complete (like the TIMED EATING trial, among any others).