European Journal of Clinical Nutrition (1999) 53, 706±710
ß 1999 Stockton Press. All rights reserved 0954±3007/99 $15.00
http://www.stockton-press.co.uk/ejcn
Breakfast glycaemic response in patients with type 2 diabetes:
Effects of bedtime dietary carbohydrates
M Axelsen1*, R Arvidsson Lenner 2, P LoÈnnroth1 and U Smith
1
1
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, S-413 45
GoÈteborg, Sweden; and 2Department of Clinical Nutrition, Department of Internal Medicine, Sahlgrenska University Hospital, GoÈteborg
University, Sweden
Objectives: Bedtime carbohydrate (CHO) intake in patients with type-2 diabetes may improve glucose tolerance
at breakfast the next morning. We examined the `overnight second-meal effect' of bedtime supplements
containing `rapid' or `slow' CHOs.
Design: Randomized cross-over study with three test-periods, each consisting of two days on a standardized diet,
followed by a breakfast tolerance test on the third morning.
Setting: The Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, GoÈteborg, Sweden.
Subjects: Sixteen patients with type 2 diabetes on oral agents and=or diet.
Interventions: Two different bedtime (22.00 h) CHO supplements (0.46 g available CHO=kg body weight) were
compared to a starch-free placebo (`normal' food regimen). The CHOs were provided as uncooked cornstarch
(slow-release CHOs) or white bread (rapid CHOs).
Results: On the mornings after different bedtime meals we found similar fasting glucose, insulin, free fatty acid
and lactate levels. However, the glycaemic response after breakfast was 21% less after uncooked cornstarch
compared to placebo ingestion at bedtime (406 46 vs 511 61 mmol min 171, P < 0.01). In contrast, it did not
differ when the evening meal consisted of white bread (451 57 mmol min 171) compared to placebo.
According to an in vitro analysis, uncooked cornstarch contained 4 times more slowly digestible starch as
compared to white bread.
Conclusions: A bedtime meal providing uncooked cornstarch improved breakfast tolerance the next morning
while, in contrast, this was not found following a bedtime meal of white bread. The results are consistent,
therefore, with the concept that an increased intake of slowly digestible carbohydrates exert an overnight secondmeal effect in patients with type 2 diabetes.
Sponsorship: This study was supported by grants from the Swedish Medical Research Council (project 3506)
and the Ingabritt and Arne Lundberg Foundation.
Descriptors: blood glucose; insulin; dietary carbohydrates; diabetes; type 2; dietary starch
Introduction
Type 2 diabetic patients exhibit important changes in
diurnal insulin sensitivity, with a more pronounced insulin
resistance in the morning as compared to in the afternoon
(Atiea et al, 1987; Dimitriadis et al, 1988; Perriello et al,
1998; Shapiro et al, 1991). This perturbation has a negative
effect on both the fasting and morning postprandial blood
*Correspondence: Dr M Axelsen, The Lundberg Laboratory for Diabetes
Research, Department of Internal Medicine, Sahlgrenska University
Hospital, S-413 45 GoÈteborg, Sweden.
Contributors: MA: conception and design; provision of study materials
and patients; administrative, technical, and logistic support; collection and
assembly of data; analysis and interpretation of data; statistics; drafting of
the article; critical revision of the article for important intellectual content.
RAL: Conception and design; administrative, technical, and logistic
support; critical revision of the article for important intellectual content.
PL: conception and design; critical revision of the article for important
intellectual content. US: Conception and design; administrative, technical,
and logistic support; analysis and interpretation of data; statistics; drafting
of the article; critical revision of the article for important intellectual
content; obtaining of funding.
Guarantor: M Axelsen and U Smith.
Received 28 January 1999; revised 26 February 26 1999; accepted 15
March 1999.
glucose concentrations (Bolli, 1988; Ferrannini et al, 1988;
Firth et al; McMahon et al, 1989; Mitrakou et al, 1990).
Finding a regimen which alleviates the insulin resistance in
the morning should, thus, be considered critically important
in the management of type 2 diabetes. The potential role of
the diet, such as timing and release pro®le of various
carbohydrates, remains to be de®ned.
The concept of a second-meal effect has attracted interest in recent years (Abraira et al, 1987; Jenkins et al, 1982;
Shaheen & Fleming, 1987; Wolever et al, 1995, 1988).
Brie¯y, it may be de®ned as the ®rst of two consecutive
carbohydrate loads leading to improved glucose tolerance
to the second. Wolever et al, (1988) showed in healthy
subjects that breakfast carbohydrate tolerance can be
improved when low-glycaemic-index foods are eaten the
previous evening. Recently, we have shown that a large
amount of bedtime carbohydrates, provided as uncooked
cornstarch, also leads to an improved glucose tolerance the
next morning in type 2 diabetic patients (Axelsen et al,
1997). However, the mechanism(s) for the overnight
second-meal effect by cornstarch ingestion were not fully
elucidated. Since uncooked cornstarch possesses a slow
release pro®le in vivo (Axelsen et al, 1999; Chen et al,
1984; Collings et al, 1981; Hayde & Widhalm, 1990;
Bedtime carbohydrates in type 2 diabetes
M Axelsen et al
Wolfsdorf & Crigler Jr, 1997), the lente characteristic of
the food may be critical in eliciting the overnight secondmeal effect in type 2 diabetic patients.
The aims of this present study, therefore, were to
examine the overnight second-meal effect of a bedtime
supplement of `rapid' and `slow' starch and to compare that
to the effect of a starch-free placebo (a `normal' mealregimen) in type 2 diabetic patients. In addition, an in vitro
analysis was undertaken to examine the content of rapidly
and slowly digestible starch in uncooked cornstarch and in
two reference foods.
Material and methods
Sixteen patients with type 2 diabetes were recruited by
means of newspaper advertisement. They had a glycated
hemoglobin A1c below 10% (ref. 3.3 ± 5.3%) and fasting
blood glucose below 12 mmol=l. None of the patients were
treated with insulin. Treatments and clinical characteristics
of the patients are shown in Table 1. All participants gave
their informed consent and the study was approved by the
Ethical Committee of GoÈteborg University.
Metabolic study
The patients were studied in three consecutive periods in
random order, with 5 ± 10 d separating each period. During
the test periods the patients adhered to a standardized diet
at home for 2 d. In the evenings at 22.00 h a bedtime meal
was taken. A meal tolerance test was performed in the
laboratory on the third morning. The standardized diet
(Table 2), which was prepared in advance, was stored at
7 18 C and thawed on the day of consumption. The energy
content was 8.4 MJ (2000 kcal), with 19% of energy (E%)
from protein, 36 E% from fat and 45 E% from carbohydrates, and the ®ber content was 46 g=d. Beverages
were standardized individually. The patients were informed
to abstain from exercise and, if applicable, to carefully
follow the prescribed times for medical treatments.
Three different bedtime meals at 22.00 h were tested
(Table 3). The uncooked cornstarch (Maizena1, CPC
Foods AB, Kristianstad, Sweden) and bread supplements
provided an identical amount of available carbohydrates,
0.46 g=kg body weight. The placebo contained only a
thickening-agent (pectin) and, hence, no available starch.
The cornstarch and placebo ingredients were pre-mixed and
dispensed in jars. In the bread period, the juice was taken
along with the bread. The meals provided the same amount
of water, and no other liquids were allowed for 1 h before
or after the meals.
The patients came to the laboratory at 07.30 h on day
three, fasting from 22.10 h the previous evening. Hypoglycaemic agents, if any, were taken at the laboratory 20 min
before being served a standard breakfast. A venous catheter
Table 1 Clinical characteristics of the patients
Sex (M=F)
Age (y)
Fasting blood glucose (mmol=l)
HbA1c(%)
BMI (kg=m2)
waist=hip-ratio
Oral agents:
Metformin (n)
Sulphonylurea (n)
14=2
61 9
8.4 1.7
6.5 0.9
29.2 5.0
0.95 0.07
Means s.d. (range), BMI; body mass index.
4
8
(40 ± 73)
(6.6 ± 11.7)
(5.0 ± 7.8)
(22.5 ± 44.2)
(0.85 ± 1.08)
707
Table 2 Standardized meals prior to the breakfast study
Weight g
Breakfast at 07.00 h
Wholemeal bread
Butter
Bologna
Beef
Orange
Snack at 10.00 h
Wholemeal bread
Butter
Ham
Lunch at 12.00 h
Day 1: Chili con carne
Day 2: Goulash
White bread
Butter
Berries
Coffee cream
Sugar
Snack at 15.30 h
Banana
Dinner at 18.00 h
Shrimps
Wholemeal bread
Butter
Mayonnaise
Pear
Evening snack at 20.00 h
Wheat-bun
70
8
15
10
105
50
5
18
300
310
50
8
100
30
10
120
200
50
8
30
110
50
Table 3 Ingredients of the bedtime meals
Placebo
g=kg body wt
Water
Low-sugar fruit juice,
dry matter
Pectin
Uncooked cornstarch
White bread
Available carbohydrates
from starch
Proteina
Fata
Cornstarch
g=kg body wt
White bread
g=kg body wt
2.00
0.12
1.67
0.12
1.67
0.12
0.033
Ð
Ð
Ð
Ð
0.55
Ð
0.46
Ð
Ð
0.96
0.46
< 0.01
< 0.01
0.08
0.03
Ð
a
Values according to food tables.
was placed in the left arm, which was kept in heating pads
to arterialize the blood. Samples were collected at 7 10
and 0 min for analysis of glucose, insulin, free fatty acids
and lactate. The standardized breakfast consisted of wholegrain bread with butter, cheese (28% butterfat) and ham
and was served at 08.00 h, with coffee or tea in a standardized amount. The calculated energy content was 2.0 MJ
(484 kcal) and 1.8 MJ (420 kcal) for males and females,
respectively, of which 14 E% were derived from protein,
40 E% from fat and 46 E% from carbohydrates. Postprandial blood samples were collected every half hour for 4 h.
Blood glucose was analyzed by an automatic glucose
analyzer (YSI, Yellow Springs Instruments, Texas). The
remaining samples were centrifuged, frozen and stored at
7 20 C until analysis. Plasma free fatty acids were determined with an enzymatic colorimetric method (Wako
Chemicals GmbH, Neuss, Germany). Plasma insulin was
determined with radioimmunochemical analyses (Pharmacia Insulin RIA, Pharmacia AB, Uppsala, Sweden) and
plasma lactate by an automatic analyzer (YSI, Yellow
Springs Instruments, Texas).
Bedtime carbohydrates in type 2 diabetes
M Axelsen et al
708
Starch analyses
A starch analysis was undertaken for: (1) white bread; (2)
uncooked cornstarch; and (3) pumpernickel-bread with
100% kernels (Schwarzbot, Delba, Delbrck, Germany).
The white bread and cornstarch samples were from the
same batch of foods used in the metabolic study. The
pumpernickel bread was included as a reference product
for a `slowly digestible' starchy food. Because the cornstarch ingredients were pre-mixed before the actual ingestion by the patients, an additional digestibility analysis was
performed on uncooked cornstarch which had been left in
water for 48 h. The amounts of rapidly digestible starch,
slowly digestible starch, resistant starch and total starch
were analyzed by in vitro enzymatic hydrolysis and the
released glucose measured by glucose oxidase (GOD-PAP,
Boehringer), as previously described (Englyst et al, 1992).
Brie¯y, chewing was mimicked by passing the bread
through a standardized mincer (0.9 cm diameter holes).
Samples were put in tubes containing pepsin, pectin,
hydrochloric acid and glass-beads and were shaken in a
water bath (37 C) for 30 min. Rapidly digestible starch
(RDS) was de®ned as the glucose released after 20 min
incubation with pancreatin (Pancrex V, Paines & Byrne,
Greenford, Middx, UK) and amyloglycosidase (EC 3.2.1.3,
Novo Norisk, Copenhagen). After a further 100 min, a
second sample was removed, de®ned as slowly digestible
starch (SDS). Total starch (TS) was de®ned as the glucose
released by complete enzymatic hydrolysis of starch after
gelatinization in boiling water and treatment with potassium hydroxide to disperse retrograded amylose. Resistant
starch (RS) was de®ned as the starch not hydrolyzed after
120 min incubation (TS 7 (RDS ‡ SDS), and available
starch (Table 3) de®ned as TS-RS.
Statistical analyses
The data are presented as means s.e.m., unless otherwise
stated. Data are expressed as fasting values, peak responses
and the incremental area under the curve above baseline
(IAUC) (Matthews et al, 1990). Statistical signi®cances
between cornstarch and placebo, and between white bread
and placebo, were evaluated by Wilcoxon's paired ranksum test. All signi®cances are two-tailed and a P-level of
< 0.05 was considered statistically signi®cant.
Results
Metabolic study
On the morning after uncooked cornstarch, white bread or
placebo at 22.00 h, similar fasting levels (08.00) of blood
glucose (8.2 0.5, 8.2 0.5 and 8.1 0.4 mmol=l), insulin
(11.9 1.4, 11.6 1.3 and 12.5 1.4 mU=l), FFA
(0.67 0.6, 0.70 0.06 and 0.69 0.06 mmol=l) and lactate
(1.1 0.1, 1.2 0.1 and 1.2 0.1 mmol=l) were obtained.
However, the IAUC for glucose after breakfast (Figure 1A)
was 21% less following cornstarch compared to placebo
consumption the previous evening (406 46 vs
511 61 mmol min 171, P < 0.01). In contrast, the postbreakfast glucose IAUC after white bread was
451 57 mmol min 171, which did not differ signi®cantly
from placebo consumption in the previous evening. The
blood glucose peak after breakfast subsequent to cornstarch
(12.0 0.5 mmol=l) was lower than the peak following
placebo consumption the previous evening (12.7 0.4 mmol=l) (P < 0.05) but, again, did not differ after
white bread (12.4 0.5 mmol=l) compared to after placebo
Figure 1 (A) Mean glucose (top) and (B) insulin (bottom) levels during a
standardized breakfast in 16 type 2 diabetic patients after ingestion at
22.00 h the previous evening of uncooked cornstarch (*) and white bread
(s) or carbohydrate free placebo (u). Vertical bars represent standard
error (SE). IAUC; area under incremental curve.
consumption. The post-breakfast IAUC or peak levels for
insulin (Figure 1B), and AUC or nadir levels for FFA (data
not shown), were similar after the different bedtime snacks.
However, the lactate IAUC after breakfast was higher
after cornstarch consumption (104 14 vs 83 14 mmol
min 171 for cornstarch and placebo, respectively, P <
0.05), but not after intake of white bread (95 24 mmol
min 171).
Starch analyses
The results from the in vitro digestibility analyses are
shown in Table 4. The total starch content per 100 g
ranged from 32 ± 89 g. Expressed as % of total starch,
rapidly digestible starch represented 88% of the starch in
white bread (Table 4). In contrast, uncooked cornstarch and
pumpernickel bread contained similarly low proportions
(38% and 48%) of rapidly digestible starch, and high
proportions (55% and 51%) of slowly digestible starch.
The contribution of resistant starch from all foods were
minor (data not shown), the highest being 6 g=100 g dryweight in uncooked cornstarch. We found no effect on
starch digestibility by soaking the cornstarch in roomtempered water for 48 h (Table 4).
Discussion
An increase in carbohydrates in the evening meal does not
affect glycaemic control the next morning in type 2 diabetic
patients (Axelsen et al, 1997; Beebe et al, 1990). However,
Bedtime carbohydrates in type 2 diabetes
M Axelsen et al
Table 4 Starch digestibility in vitro
Types of starcha
Rapidly digestible Slowly digestible
Total
starch
starch
starch (TS)
g=100 g (% of TS) g=100 g (% of TS)
Uncooked cornstarch,
dry
Uncooked cornstarch
wet for 48 h
White bread
Pumpernickel bread
g=100 g
34.3
(38%)
49.2
(55%)
89.1
31.3
(35%)
51.5
(57%)
89.7
42.1
15.6
(88%)
(48%)
5.8
16.5
(12%)
(51%)
47.9
32.2
a
Resistant starch not shown.
we speculated that this is due to the carbohydrates being
supplied by `rapid' foods. White bread is, by de®nition
(Wolever et al, 1991), a high glycaemic food. The novel
®nding of this present study is that a bedtime meal providing carbohydrates from uncooked cornstarch positively
affected breakfast tolerance the next morning while, in
contrast, this was not found following a bedtime meal
consisting of white bread. According to the in vitro analysis, uncooked cornstarch had a similar release pro®le as
pumpernickel bread, a well-recognized `slow' food (Jenkins et al, 1986). The data, thus, suggest the importance of
a slow release pro®le of the carbohydrates in eliciting an
overnight second-meal effect in type 2 diabetic patients.
The purpose of this present study was to de®ne the
preferable kind of carbohydrates a dietary supplement
should contain in order to exert an overnight second-meal
effect in type 2 diabetics. The results were consistent with
the concept that slowly digestible carbohydrates exert a
second-meal effect. In addition to types of carbohydrates,
the amounts used are probably also of importance. In both
the white bread and cornstarch periods, the amounts of
carbohydrates were increased compared to the `normal'
period. In contrast, when comparing the glycaemic
response after breakfast in the white bread and cornstarch
periods, it tended to be less after cornstarch than after bread
but this effect was less pronounced than compared to the
normal meal regimen (Figure 1). However, it may be
argued that the high fat content of the breakfast meal
(40% of the energy) may diminish the `glucotoxic' effect
of high glucose peaks, due to inhibition of the gastric
emptying (Cunningham & Read, 1989). If so, the bene®cial
effect of cornstarch compared to white bread may be larger
than that demonstrated here.
The factor(s) responsible for the overnight second-meal
effect have not yet been established. Free fatty acids have a
number of effects, such as decreased peripheral glucose
disposal (Boden & Chen, 1995; Groop et al, 1989), a
`lipotoxic' effect on pancreatic insulin release (BjoÈrklund
et al, 1997; Paolisso et al, 1998) and an increased endogenous glucose production (Golay et al, 1987; Saloranta et
al, 1991), all of which are present in type 2 diabetic
patients. Wolever et al (1995) showed in healthy subjects
that the second-meal effect is associated with reduced free
fatty acid levels before and after the second meal. In
addition, we found in type 2 diabetic patients, that the
free fatty acid levels late at night (2 ± 7 am) were reduced
after increased intake at bedtime of `slow' carbohydrates
( 50 g) at 22.00 h, while this was not found after increased
intake of similar amounts of `rapid' carbohydrates (Axelsen
et al, unpublished observations).
The clinical implications of this present study remain to
be shown. A bedtime carbohydrate supplement will raise
the nocturnal glucose levels, clearly an unwanted change in
type 2 diabetic patients. However, a low dose ( 25 g) also
elicits bene®cial effects on morning glucose metabolism, at
least in patients with well-preserved endogenous insulin
secretion (Axelsen et al, unpublished observations). Hence
a temporal change in carbohydrate intake, whereby the
bene®cial effects of a diminished breakfast carbohydrate
content (Stilling et al, 1998) are combined with a bedtime
slow-release carbohydrate supplement, may be worthy of
study in type 2 diabetic patients. In addition, a lipotoxic
effect of free fatty acids on the pancreatic insulin release
(Shimabukuro et al, 1998) and an elevated endogenous
glucose production (Perriello et al, 1988) are present also in
obese patients with impaired glucose tolerance. Whether
bedtime intake or slow-release carbohydrates may alleviate
these perturbations and, therefore, prevent or delay the
development of manifest diabetes in these individuals, is
an intriguing possibility that warrants further studies.
Conclusions
A bedtime meal providing carbohydrates from uncooked
cornstarch positively affects the glucose tolerance the next
morning in type 2 diabetic patients, while this effect is not
achieved with a bedtime meal consisting of white bread.
Uncooked cornstarch contain half the amount of rapidly
digestible carbohydrates but 4 times more slowly digestible starch as compared to white bread. The results are
consistent, therefore, with the concept that an increased
intake of slowly digestible carbohydrates exerts an overnight second-meal effect in patients with type 2 diabetes.
References
Abraira C, Buchanan B & Hodges L (1987): Modi®cation of glycogen
deposition by priming glucose loads: the second-meal phenomenon.
Am. J. Clin. Nutr. 45, 952 ± 957.
Atiea J, Ryder R, Vora J, Owens D, Luzio S, Williams S & Hayes T
(1987): Dawn phenomenon: Its frequency in non-insulin-dependent
diabetic patients on conventional therapy. Diabetes Care 10, 461 ± 465.
Axelsen M, LoÈnnroth P, Arvidsson Lenner R & Smith U (1997):
Suppression of the nocturnal free fatty acid levels by bedtime cornstarch
in NIDDM. Eur. J. Clin. Invest. 27, 157 ± 163.
Axelsen M, Wesslau C, Arvidsson Lenner R, LoÈnnroth P &; Smith U
(1999): Bedtime uncooked cornstarch supplement prevents nocturnal
hypoglycaemia in intensively treated IDDM subject. J. Intern. Med.
245, 229 ± 236.
Beebe C, Van Cauter E, Shapiro E, Tillil H Lyons R, Rubenstein A &
Polonsky K (1990): Effect of temporal distribution of calories on
diurnal patterns of glucose levels and insulin secretion in NIDDM.
Diabetes Care 13, 748 ± 755.
BjoÈrklund A, Yaney G, McGarry J & Weir G (1997): Fatty acids and betacell function. Diabetologia 40, B21 ± B26.
Boden G & Chen X (1995): Effects of fat on glucose uptake and utilization
in patients with non-insulin-dependent diabetes. J. Clin. Invest 96,
1261 ± 1268.
Bolli G (1988): The dawn phenomenon: Its origin and contribution to early
morning hyperglycemia in diabetes mellitus. Diabete & Metabolism 14,
675 ± 686.
Chen Y, Cornblath M & Sidbury J (1984): Cornstarch therapy in type 1
glycogen storage disease. N. Engl. J. Med. 310, 171 ± 175.
Collings P, Williams C & Macdonald I (1981): Effects of cooking on
serum glucose and insulin responses to starch. Br. Med. J. 282, 1032.
Cunningham K & Read N (1989): The effect of incorporating fat into
different components of a meal on gastric emptying and postprandial
blood glucose and insulin responses. Br. J. Nutr. 61, 285 ± 190.
Dimitriadis G, Vlachonikolis I, Hatziagellaki E, Linos A, Kordonouri O,
Alexopoulos E & Raptis S (1988): The `dawn phenomenon' in patients
with type II diabetes mellitus. Diabetes Nutr. Metab. 1, 37 ± 41.
709
Bedtime carbohydrates in type 2 diabetes
M Axelsen et al
710
Englyst H, Kingman S & Cummings J (1992): Classi®cation and measurement of nutritionally important starch fractions. Eur. J. Clin. Nutr. 46,
Suppl 2, S33 ± S50.
Ferrannini E, Simonson D, Katz L, Reichard G, Bevilacqua S, Barret E,
Olsson M & DeFronzo R (1988): The disposal of an oral glucose load in
patients with non-insulin-dependent diabetes. Metabolism 47, 79 ± 85.
Firth R, Bell P, March H, Hansen I & Rizza R (1986): Postprandial
hyperglycemia in patients with noninsulin-dependent diabetes mellitus:
roles of hepatic and extra-hepatic tissues. J. Clin. Invest. 77, 1525 ± 1532.
Golay A, Swislocki A, Chen Y-D & Reaven G (1987): Relationships
between plasma-free fatty acid concentration, endogenous glucose
production, and fasting hyperglycemia in normal and non-insulindependent diabetic individuals. Metabolism 36, 692 ± 696.
Groop L, Bonadonna R, Del Prato S, Ratheiser K, Zyck K, Ferrannini E &
DeFronzo R (1989): Glucose and free fatty acid metabolism in noninsulin dependent diabetes mellitus. Evidence for multiple sites of
insulin resistance. J. Clin. Invest. 84, 205 ± 213.
Hayde M & Widhalm K (1990): Effects of cornstarch treatment in very
young children with type I glycogen storage disease. Eur. J. Pediatr.
149, 630 ± 633.
Jenkins D, Wolever T, Jenkins A, Giordano C, Giudici S, Thompson L,
Kalmusky J, Josse R & Wong G (1986): Low glycemic response to
traditionally processed wheat and rye products: bulgur and pumpernickel bread. Am. J. Clin. Nutr. 43, 516 ± 520.
Jenkins D, Wolever T, Taylor R, Grif®ths C, Krzeminska K, Lawrie J,
Bennett C, Goff D, Sarson D & Bloom S (1982): Slow release carbohydrate improves second meal tolerance. Am. J. Clin. Nutr. 35, 1339 ± 1346.
Matthews J, Altman D, Campbell M & Royston P (1990): Analysis of
serial measurements in medical research. Br. Med. J. 300, 230 ± 235.
McMahon M, Marsh H & Rizza R (1989): Effects of basal insulin
supplementation on the disposition of a mixed meal in obese patients
with non-insulin-dependent diabetes mellitus. Diabetes 38, 291 ± 303.
Mitrakou A, Kelley D, Veneman T, Jenssen T, Pangburn T, Reilly J &
Gerich J (1990): Contribution of abnormal muscle and liver glucose
metabolism to postprandial hyperglycemia in NIDDM. Diabetes 39,
1381 ± 1390.
Paolisso G, Tagliamonte M, Rizzo M, Gualdiero P. Saccomanno F,
Gambardella A, Giugliano D, Onofrio F & Howard B (1988): Lowering
fatty acids potentiates acute insulin response in ®rst degree relatives of
people with type II diabetes. Diabetologia 41, 1127 ± 1132.
Perriello G, DeFeo P, Torlone E, Fanelli C, Santeusanio F, Brunetti P &
Bolli G (1988): Early night exaggerated hepatic glucose production,
later reduction of glucose clearance, and non-responsiveness of b-cell
all contribute to abnormal postabsorptive glucose homeostasis in subjects with impaired glucose tolerance. Second EASD Satellite Symposium on control of Metabolism, Lyon 2 ± 3 Sept., 1988.
Perriello G, Pimenta W, Pampanelli S, Porcellati F, Lepore M, Lucidi P,
Cordoni M, Brunetti P & Bolli G (1988): Evidence of day-night changes
in insulin sensitivity in type 2 diabetes mellitus (abstract). Diabetologia
41, Suppl 1, A194.
Saloranta C, Franssila-Kallunki A, Ekstrand A, Taskinen M-R & Groop L
(1991): Modulation of hepatic glucose production by non-esteri®ed
fatty acids in type II (non-insulin-dependent) diabetes mellitus. Diabetologia 34, 409 ± 415.
Shaheen S & Fleming S (1987): High-®ber foods at breakfast: in¯uence on
plasma glucose and insulin responses to lunch. Am. J. Clin. Nutr. 46,
804 ± 811.
Shapiro E, Polonsky K, Copinschi G, Bosson D, Tillil H, Blackman J,
Lewis G & VanCauter E (1991): Nocturnal elevation of glucose levels
during fasting in noninsulin-dependent diabetes. J. Clin. Endocr. Metab.
72, 444 ± 454.
Shimabukuro M, Zhou Y-T, Levi M & Unger R (1998): Fatty acid-induced
b cell apoptosis: A link between obesity and diabetes. Proc. Natl. Acad.
Sci. 95, 2498 ± 2502.
Stilling B, Mehlsen J, Hamberg O, Larsen J, Gram N & Madsbad S (1998):
Effect of starch-free bread on metabolic control in type 2 diabetes
[letter]. Lancet 352, 369 ± 370.
Wolever T, Bentum-Williams A & Jenkins D (1995): Physiological
modulation of plasma free fatty acid concentration by diet: implications
in non-diabetic subjects. Diabetes Care 18, 962 ± 970.
Wolever T, Jenkins D, Jenkins A & Josse R (1991): The glycemic
index: methodology and clinical implications. Am. J. Clin. Nutr. 54,
846 ± 854.
Wolever T, Jenkins D, Ocana A, Rao V & Collier G (1988): Secondmeal effect: low-glycemic-index foods eaten at dinner improve
subsequent breakfast glycemic response. Am. J. Clin. Nutr. 48,
1041 ± 1047.
Wolfsdorf J & Crigler Jr J (1997): Cornstarch regimens for nocturnal
treatment of young adults with type I glycogen storage disease. Am. J.
Clin. Nutr. 65, 1507 ± 1511.